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Han S, Lu M, Zhang Y, Lin Y, Liu Q, Xu L, Ren Z. Modification Effects of Homologous Recombination Repair Gene Polymorphisms on the Associations Between Urinary Metals and Breast Cancer Risk. Biol Trace Elem Res 2025; 203:694-706. [PMID: 38720017 DOI: 10.1007/s12011-024-04215-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 04/28/2024] [Indexed: 01/22/2025]
Abstract
Metals are recognized as important factors related to breast cancer (BC) risk. Homologous recombination repair (HRR) genes might modify the toxicity of metals by influencing the distribution and metabolism of metal compounds. This study aims to investigate the modification effects of single nucleotide polymorphisms (SNPs) in HRR genes on the associations between urinary metals and BC risk. A total of 685 BC cases and 741 controls were recruited from October 2009 to December 2012. Twenty-one metals were analyzed in urine samples using inductively coupled plasma mass spectrometry (ICP-MS), and three SNPs (LIG3 rs1052536, RFC1 rs6829064, and RAD54L rs17102086) were genotyped. We identified significant interactions between four metals and two SNPs on the risk of BC. For LIG3 rs1052536 C/T variant, participants with CT/TT genotypes exposed to higher cobalt (Co) levels had higher BC risk compared to those with CC genotype (Pinteraction = 0.048). For RAD54L rs17102086 T/C variant, participants with TT genotype who were exposed to higher levels of zinc (Zn), Co, arsenic (As), and strontium (Sr) had more pronounced BC risk than the CC/TC genotypes (all Pinteraction < 0.05). This study showed compelling evidence for the interaction between genetic variants within the HRR system and urinary metals on BC risk. Our findings highlight the need to consider genetic makeup when evaluating the carcinogenic or protective potential of metals.
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Affiliation(s)
- Shushu Han
- The School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China
| | - Minjie Lu
- The School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China
| | - Yixin Zhang
- The School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China
| | - Ying Lin
- The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Qiang Liu
- The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Lin Xu
- The School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China.
| | - Zefang Ren
- The School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China.
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Chen HW, Kuo WH, Lu YS, Chen IC, Hu FC, Wang MY, Zahid M, Rogan EG, Cheng AL, Lin CH. Interaction of base excision repair gene polymorphism and estrogen-DNA adducts in breast cancer risk among East Asian women. Breast Cancer Res Treat 2024; 208:283-292. [PMID: 38969945 DOI: 10.1007/s10549-024-07418-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 06/27/2024] [Indexed: 07/07/2024]
Abstract
PURPOSE In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. METHODS We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. RESULTS Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). CONCLUSION APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.
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Affiliation(s)
- Hsing-Wu Chen
- Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan
| | - Wen-Hung Kuo
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Shen Lu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan
| | - I-Chun Chen
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan
- Department of Medical Oncology, National Taiwan University Hospital, Cancer Center Branch, Taipei, Taiwan
| | - Fu-Chang Hu
- Graduate Institute of Clinical Medicine and School of Nursing, College of Medicine, National Taiwan University, Taipei, Taiwan
- Statistical Consulting Clinic, International-Harvard Statistical Consulting Company, Taipei, Taiwan
| | - Ming-Yang Wang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Muhammad Zahid
- Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Eleanor G Rogan
- Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Oncology, National Taiwan University Hospital, Cancer Center Branch, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ching-Hung Lin
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
- Department of Medical Oncology, National Taiwan University Hospital, Cancer Center Branch, Taipei, Taiwan.
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
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Young CL, Beichman AC, Mas Ponte D, Hemker SL, Zhu L, Kitzman JO, Shirts BH, Harris K. A maternal germline mutator phenotype in a family affected by heritable colorectal cancer. Genetics 2024; 228:iyae166. [PMID: 39403956 PMCID: PMC11631438 DOI: 10.1093/genetics/iyae166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 10/11/2024] [Indexed: 10/23/2024] Open
Abstract
Variation in DNA repair genes can increase cancer risk by elevating the rate of oncogenic mutation. Defects in one such gene, MUTYH, are known to elevate the incidence of colorectal cancer in a recessive Mendelian manner. Recent evidence has also linked MUTYH to a mutator phenotype affecting normal somatic cells as well as the female germline. Here, we use whole genome sequencing to measure germline de novo mutation rates in a large extended family containing both mothers and fathers who are affected by pathogenic MUTYH variation. By developing novel methodology that uses siblings as "surrogate parents" to identify de novo mutations, we were able to include mutation data from several children whose parents were unavailable for sequencing. In the children of mothers affected by the pathogenic MUTYH genotype p.Y179C/V234M, we identify an elevation of the C>A mutation rate that is weaker than mutator effects previously reported to be caused by other pathogenic MUTYH genotypes, suggesting that mutation rates in normal tissues may be useful for classifying cancer-associated variation along a continuum of severity. Surprisingly, we detect no significant elevation of the C>A mutation rate in children born to a father with the same MUTYH genotype, and we similarly find that the mutator effect of the mouse homolog Mutyh appears to be localized to embryonic development, not the spermatocytes. Our results suggest that maternal MUTYH variants can cause germline mutations by attenuating the repair of oxidative DNA damage in the early embryo.
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Affiliation(s)
- Candice L Young
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
- Department of Molecular and Cellular Biology, University of Washington, 1705 NE Pacific St, Seattle, WA 98195, USA
| | - Annabel C Beichman
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
| | - David Mas Ponte
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
| | - Shelby L Hemker
- Department of Human Genetics, University of Michigan, 1241 Catherine St, Ann Arbor, MI 48109, USA
| | - Luke Zhu
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
- Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
| | - Jacob O Kitzman
- Department of Human Genetics, University of Michigan, 1241 Catherine St, Ann Arbor, MI 48109, USA
| | - Brian H Shirts
- Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA
| | - Kelley Harris
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
- Herbold Computational Biology Program, Fred Hutchinson Cancer Center, P.O. Box 19024, Seattle, WA 98109, USA
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Young CL, Beichman AC, Mas-Ponte D, Hemker SL, Zhu L, Kitzman JO, Shirts BH, Harris K. A maternal germline mutator phenotype in a family affected by heritable colorectal cancer. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2023.12.08.23299304. [PMID: 38196581 PMCID: PMC10775336 DOI: 10.1101/2023.12.08.23299304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
Variation in DNA repair genes can increase cancer risk by elevating the rate of oncogenic mutation. Defects in one such gene, MUTYH, are known to elevate the incidence of colorectal cancer in a recessive Mendelian manner. Recent evidence has also linked MUTYH to a mutator phenotype affecting normal somatic cells as well as the female germline. Here, we use whole genome sequencing to measure germline de novo mutation rates in a large extended family containing both mothers and fathers who are affected by pathogenic MUTYH variation. By developing novel methodology that uses siblings as "surrogate parents" to identify de novo mutations, we were able to include mutation data from several children whose parents were unavailable for sequencing. In the children of mothers affected by the pathogenic MUTYH genotype p.Y179C/V234M, we identify an elevation of the C>A mutation rate that is weaker than mutator effects previously reported to be caused by other pathogenic MUTYH genotypes, suggesting that mutation rates in normal tissues may be useful for classifying cancer-associated variation along a continuum of severity. Surprisingly, we detect no significant elevation of the C>A mutation rate in children born to a father with the same MUTYH genotype, and we similarly find that the mutator effect of the mouse homolog Mutyh appears to be localized to embryonic development, not the spermatocytes. Our results suggest that maternal MUTYH variants can cause germline mutations by attenuating the repair of oxidative DNA damage in the early embryo.
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Affiliation(s)
- Candice L. Young
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195
- Department of Molecular and Cellular Biology, University of Washington, 1705 NE Pacific St, Seattle, WA 98195
| | - Annabel C. Beichman
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195
| | - David Mas-Ponte
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195
| | - Shelby L. Hemker
- Department of Human Genetics, University of Michigan, 1241 Catherine St, Ann Arbor, MI 48109
| | - Luke Zhu
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195
- Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98195
| | - Jacob O. Kitzman
- Department of Human Genetics, University of Michigan, 1241 Catherine St, Ann Arbor, MI 48109
| | - Brian H. Shirts
- Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195
| | - Kelley Harris
- Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195
- Herbold Computational Biology Program, Fred Hutchinson Cancer Center, P.O. Box 19024, Seattle, WA 98109
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Li J, Jia Z, Dong L, Cao H, Huang Y, Xu H, Xie Z, Jiang Y, Wang X, Liu J. DNA damage response in breast cancer and its significant role in guiding novel precise therapies. Biomark Res 2024; 12:111. [PMID: 39334297 PMCID: PMC11437670 DOI: 10.1186/s40364-024-00653-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
DNA damage response (DDR) deficiency has been one of the emerging targets in treating breast cancer in recent years. On the one hand, DDR coordinates cell cycle and signal transduction, whose dysfunction may lead to cell apoptosis, genomic instability, and tumor development. Conversely, DDR deficiency is an intrinsic feature of tumors that underlies their response to treatments that inflict DNA damage. In this review, we systematically explore various mechanisms of DDR, the rationale and research advances in DDR-targeted drugs in breast cancer, and discuss the challenges in its clinical applications. Notably, poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated favorable efficacy and safety in breast cancer with high homogenous recombination deficiency (HRD) status in a series of clinical trials. Moreover, several studies on novel DDR-related molecules are actively exploring to target tumors that become resistant to PARP inhibition. Before further clinical application of new regimens or drugs, novel and standardized biomarkers are needed to develop for accurately characterizing the benefit population and predicting efficacy. Despite the promising efficacy of DDR-related treatments, challenges of off-target toxicity and drug resistance need to be addressed. Strategies to overcome drug resistance await further exploration on DDR mechanisms, and combined targeted drugs or immunotherapy will hopefully provide more precise or combined strategies and expand potential responsive populations.
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Affiliation(s)
- Jiayi Li
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
- School of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
| | - Ziqi Jia
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Lin Dong
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Heng Cao
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yansong Huang
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
- School of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
| | - Hengyi Xu
- School of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhixuan Xie
- School of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
| | - Yiwen Jiang
- School of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
| | - Xiang Wang
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jiaqi Liu
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Tufail M. DNA repair pathways in breast cancer: from mechanisms to clinical applications. Breast Cancer Res Treat 2023:10.1007/s10549-023-06995-z. [PMID: 37289340 DOI: 10.1007/s10549-023-06995-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/25/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND Breast cancer (BC) is a complex disease with various subtypes and genetic alterations that impact DNA repair pathways. Understanding these pathways is essential for developing effective treatments and improving patient outcomes. AREA COVERED This study investigates the significance of DNA repair pathways in breast cancer, specifically focusing on various pathways such as nucleotide excision repair, base excision repair, mismatch repair, homologous recombination repair, non-homologous end joining, fanconi anemia pathway, translesion synthesis, direct repair, and DNA damage tolerance. The study also examines the role of these pathways in breast cancer resistance and explores their potential as targets for cancer treatment. CONCLUSION Recent advances in targeted therapies have shown promise in exploiting DNA repair pathways for BC treatment. However, much research is needed to improve the efficacy of these therapies and identify new targets. Additionally, personalized treatments that target specific DNA repair pathways based on tumor subtype or genetic profile are being developed. Advances in genomics and imaging technologies can potentially improve patient stratification and identify biomarkers of treatment response. However, many challenges remain, including toxicity, resistance, and the need for more personalized treatments. Continued research and development in this field could significantly improve BC treatment.
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Affiliation(s)
- Muhammad Tufail
- Institute of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China.
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7
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Nunziato M, Di Maggio F, Pensabene M, Esposito MV, Starnone F, De Angelis C, Calabrese A, D’Aiuto M, Botti G, De Placido S, D’Argenio V, Salvatore F. Multi-gene panel testing increases germline predisposing mutations’ detection in a cohort of breast/ovarian cancer patients from Southern Italy. Front Med (Lausanne) 2022; 9:894358. [PMID: 36035419 PMCID: PMC9403188 DOI: 10.3389/fmed.2022.894358] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
Breast cancer is the most common neoplasia in females worldwide, about 10% being hereditary/familial and due to DNA variants in cancer-predisposing genes, such as the highly penetrant BRCA1/BRCA2 genes. However, their variants explain up to 25% of the suspected hereditary/familial cases. The availability of NGS methodologies has prompted research in this field. With the aim to improve the diagnostic sensitivity of molecular testing, a custom designed panel of 44 genes, including also non-coding regions and 5’ and 3’ UTR regions, was set up. Here, are reported the results obtained in a cohort of 64 patients, including also few males, from Southern Italy. All patients had a positive personal and/or familial history for breast and other cancers, but tested negative to routine BRCA analysis. After obtaining their written informed consent, a genomic DNA sample/patient was used to obtain an enriched DNA library, then analyzed by NGS. Sequencing data analysis allowed the identification of pathogenic variants in 12 of tested patients (19%). Interestingly, MUTYH was the most frequently altered gene, followed by RNASEL, ATM, MSH6, MRE11A, and PALB2 genes. The reported resultsreinforce the need for enlarged molecular testing beyond BRCA genes, at least in patients with a personal and familial history, strongly suggestive for a hereditary/familial form. This gives also a hint to pursue more specific precision oncology therapy.
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Affiliation(s)
- Marcella Nunziato
- CEINGE–Biotecnologie Avanzate, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
| | - Federica Di Maggio
- CEINGE–Biotecnologie Avanzate, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
| | - Matilde Pensabene
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Maria Valeria Esposito
- CEINGE–Biotecnologie Avanzate, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
| | - Flavio Starnone
- CEINGE–Biotecnologie Avanzate, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
| | - Carmine De Angelis
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
- Department of Oncology and Hematology, Regional Reference Center for Rare Tumors, Azienda Ospedaliera Universitaria (AOU) Federico II of Naples, Naples, Italy
| | - Alessandra Calabrese
- Division of Breast Surgery, Department of Breast Disease, National Cancer Institute, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) “Fondazione G. Pascale,”Naples, Italy
| | - Massimiliano D’Aiuto
- Clinica Villa Fiorita, Aversa, Italy
- Division of Breast Oncology, National Cancer Institute, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) “Fondazione G. Pascale,”Naples, Italy
| | - Gerardo Botti
- Scientific Directorate, National Cancer Institute, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) “Fondazione G. Pascale,”Naples, Italy
| | - Sabino De Placido
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
- Department of Oncology and Hematology, Regional Reference Center for Rare Tumors, Azienda Ospedaliera Universitaria (AOU) Federico II of Naples, Naples, Italy
| | - Valeria D’Argenio
- CEINGE–Biotecnologie Avanzate, Naples, Italy
- Department of Human Sciences and Quality of Life Promotion, San Raffaele Open University, Rome, Italy
- *Correspondence: Valeria D’Argenio,
| | - Francesco Salvatore
- CEINGE–Biotecnologie Avanzate, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
- Francesco Salvatore,
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MUTYH-associated tumor syndrome: The other face of MAP. Oncogene 2022; 41:2531-2539. [DOI: 10.1038/s41388-022-02304-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/23/2022] [Accepted: 03/29/2022] [Indexed: 12/13/2022]
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Zhou J, Zhou XA, Zhang N, Wang J. Evolving insights: how DNA repair pathways impact cancer evolution. Cancer Biol Med 2020; 17:805-827. [PMID: 33299637 PMCID: PMC7721097 DOI: 10.20892/j.issn.2095-3941.2020.0177] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 07/10/2020] [Indexed: 12/17/2022] Open
Abstract
Viewing cancer as a large, evolving population of heterogeneous cells is a common perspective. Because genomic instability is one of the fundamental features of cancer, this intrinsic tendency of genomic variation leads to striking intratumor heterogeneity and functions during the process of cancer formation, development, metastasis, and relapse. With the increased mutation rate and abundant diversity of the gene pool, this heterogeneity leads to cancer evolution, which is the major obstacle in the clinical treatment of cancer. Cells rely on the integrity of DNA repair machineries to maintain genomic stability, but these machineries often do not function properly in cancer cells. The deficiency of DNA repair could contribute to the generation of cancer genomic instability, and ultimately promote cancer evolution. With the rapid advance of new technologies, such as single-cell sequencing in recent years, we have the opportunity to better understand the specific processes and mechanisms of cancer evolution, and its relationship with DNA repair. Here, we review recent findings on how DNA repair affects cancer evolution, and discuss how these mechanisms provide the basis for critical clinical challenges and therapeutic applications.
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Affiliation(s)
- Jiadong Zhou
- Department of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Xiao Albert Zhou
- Department of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Ning Zhang
- Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.,Biomedical Pioneering Innovation Center (BIOPIC) and Translational Cancer Research Center, School of Life Sciences, First Hospital, Peking University, Beijing 100871, China
| | - Jiadong Wang
- Department of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
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Curia MC, Catalano T, Aceto GM. MUTYH: Not just polyposis. World J Clin Oncol 2020; 11:428-449. [PMID: 32821650 PMCID: PMC7407923 DOI: 10.5306/wjco.v11.i7.428] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/08/2020] [Accepted: 05/27/2020] [Indexed: 02/06/2023] Open
Abstract
MUTYH is a base excision repair enzyme, it plays a crucial role in the correction of DNA errors from guanine oxidation and may be considered a cell protective factor. In humans it is an adenine DNA glycosylase that removes adenine misincorporated in 7,8-dihydro-8-oxoguanine (8-oxoG) pairs, inducing G:C to T:A transversions. MUTYH functionally cooperates with OGG1 that eliminates 8-oxodG derived from excessive reactive oxygen species production. MUTYH mutations have been linked to MUTYH associated polyposis syndrome (MAP), an autosomal recessive disorder characterized by multiple colorectal adenomas. MAP patients show a greatly increased lifetime risk for gastrointestinal cancers. The cancer risk in mono-allelic carriers associated with one MUTYH mutant allele is controversial and it remains to be clarified whether the altered functions of this protein may have a pathophysiological involvement in other diseases besides familial gastrointestinal diseases. This review evaluates the role of MUTYH, focusing on current studies of human neoplastic and non-neoplastic diseases different to colon polyposis and colorectal cancer. This will provide novel insights into the understanding of the molecular basis underlying MUTYH-related pathogenesis. Furthermore, we describe the association between MUTYH single nucleotide polymorphisms (SNPs) and different cancer and non-cancer diseases. We address the utility to increase our knowledge regarding MUTYH in the light of recent advances in the literature with the aim of a better understanding of the potential for identifying new therapeutic targets. Considering the multiple functions and interactions of MUTYH protein, its involvement in pathologies based on oxidative stress damage could be hypothesized. Although the development of extraintestinal cancer in MUTYH heterozygotes is not completely defined, the risk for malignancies of the duodenum, ovary, and bladder is also increased as well as the onset of benign and malignant endocrine tumors. The presence of MUTYH pathogenic variants is an independent predictor of poor prognosis in sporadic gastric cancer and in salivary gland secretory carcinoma, while its inhibition has been shown to reduce the survival of pancreatic ductal adenocarcinoma cells. Furthermore, some MUTYH SNPs have been associated with lung, hepatocellular and cervical cancer risk. An additional role of MUTYH seems to contribute to the prevention of numerous other disorders with an inflammatory/degenerative basis, including neurological and ocular diseases. Finally, it is interesting to note that MUTYH could be a new therapeutic target and future studies will shed light on its specific functions in the prevention of diseases and in the improvement of the chemo-sensitivity of cancer cells.
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Affiliation(s)
- Maria Cristina Curia
- Department of Medical, Oral and Biotechnological Sciences, “G. d'Annunzio” University of Chieti-Pescara, Chieti, Via dei Vestini 66100, Italy
| | - Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Via Consolare Valeria 98125, Italy
| | - Gitana Maria Aceto
- Department of Medical, Oral and Biotechnological Sciences, “G. d'Annunzio” University of Chieti-Pescara, Chieti, Via dei Vestini 66100, Italy
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Floris M, Sanna D, Castiglia P, Putzu C, Sanna V, Pazzola A, De Miglio MR, Sanges F, Pira G, Azara A, Lampis E, Serra A, Carru C, Steri M, Costanza F, Bisail M, Muroni MR. MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer: a case-control study in a population from North Sardinia. BMC Cancer 2020; 20:234. [PMID: 32192442 PMCID: PMC7083022 DOI: 10.1186/s12885-020-06749-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 03/12/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Despite conflicting results, considerable evidence suggests the association between single nucleotide polymorphisms in MTHFR, XRCC1 and OGG1 genes and, risk of developing breast cancer. Here a case-control study is reported, including 135 breat cancer patients and 112 healthy women, all representative of Northern Sardinian population. METHODS Polymerase chain reaction/restriction fragment length polymorphism method was used to determine the genotypes of five polymorphisms: MTHFR C677T (rs1801133) and A1298C (rs1801131), XRCC1 Arg194Trp (rs1799782) and Arg399Gln (rs25487) and OGG1 Ser326Cys (rs1052133). Allelic, genotypic and haplotype association analyses with disease risk and clinicopathological parameters were performed. RESULTS A nominally significant association with breast cancer risk was observed for MTHFR C677T polymorphism heterozygous genotype in the codominant model (OR: 0.57, 95% CI: 0.32-1.00, p = 0.049) and for Cys/Cys genotype of the OGG1 Ser326Cys polymorphism in the recessive model (OR: 0.23, 95% CI: 0.05-1.11, p = 0.0465). No significant differences were found at genotype-level for A1298C polymorphism of the MTHFR gene and Arg194Trp and Arg399Gln of the XRCC1 gene. Furthermore, the OGG1 and XRCC1 rs25487 polymorphisms were nominally associated with PgR, Her2 status and with sporadic breast cancer, respectively. CONCLUSIONS Based on genetic characteristics of individuals included in this study, results suggest that MTHFR CT and OGG1 Cys/Cys genotypes have a protective effect that may have an influence on breast cancer risk in a representative Northern Sardinian population.
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Affiliation(s)
- Matteo Floris
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
| | - Daria Sanna
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Paolo Castiglia
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Carlo Putzu
- Division of Medical Oncology, AOU Sassari, Sassari, Italy
| | - Valeria Sanna
- Division of Medical Oncology, AOU Sassari, Sassari, Italy
| | | | - Maria Rosaria De Miglio
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Francesca Sanges
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Giovanna Pira
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Antonio Azara
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Emanuele Lampis
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | | | - Ciriaco Carru
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Maristella Steri
- Institute for Genetic and Biomedical Research, National Research Council (CNR), Monserrato, Cagliari, Italy
| | - Flavia Costanza
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | | | - Maria Rosaria Muroni
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.
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12
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Abduljaleel Z. Structural and Functional Analysis of human lung cancer risk associated hOGG1 variant Ser326Cys in DNA repair gene by molecular dynamics simulation. Noncoding RNA Res 2019; 4:109-119. [PMID: 31891019 PMCID: PMC6926185 DOI: 10.1016/j.ncrna.2019.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 10/16/2019] [Accepted: 10/16/2019] [Indexed: 12/29/2022] Open
Abstract
Oxidative damaged DNA base lesions are repaired through human 8-oxoguanine DNA glycosylase gene (hOGG1) mediated pathways. A recent report based on the meta-analysis has suggested that the DNA Repair Gene hOGG1 variant Ser326Cys [3p26.2; allele S/C in nucleotide position αHelix2 Ser⇒Cys326] was associated with Lung Cancer risk in Caucasian population will alter the level Zhong et al., 2012. To the best of our knowledge, there has not been any such comprehensive in-silico investigation that validates the functional and structural impact of non-synonymous Lung Cancer Risk Associated Protein Domain (LCRAPD) mutation Ser326Cys (rs1052133) by molecular dynamics (MD) simulation approach following prediction of hOGG1 protein before and after the mutation. Further to the native and mutant protein structures, the amino acid residue and its secondary structure were observed through a solvent accessibility model for protein stability confirmation at the point of mutation. Taken together, this study suggests that the protein functional and structural studies could be a reasonable approach for investigating the impact of nsSNPs in future studies. In addition, 4295 patients samples incorporate with the analysis that genomic data types from cBioPortal. In the result, 4295 cases (91.5%) had alterations in all genes but the frequency of alterations in our targeted hOGG1 gene was shown with and without case alteration in the ratio (Logrank Test P-Value: 0.670) Kaplan-Meier by the number of patients at risk of the survival function.
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Affiliation(s)
- Zainularifeen Abduljaleel
- Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box: 715, Makkah, 21955, Saudi Arabia.,Science and Technology Unit, Umm Al-Qura University, P.O. Box: 715, Makkah, 21955, Saudi Arabia.,Bircham International University, Av. Sierra, 2, 28691, Villanueva de La Cañada, Madrid, Spain
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13
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Hua RX, Zhuo Z, Zhu J, Zhang SD, Xue WQ, Li XZ, He J, Jia WH. LIG3 gene polymorphisms and risk of gastric cancer in a Southern Chinese population. Gene 2019; 705:90-94. [PMID: 31034940 DOI: 10.1016/j.gene.2019.04.072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 04/07/2019] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
DNA ligase III (LIG3) has been implicated in the etiology of cancer. However, few studies have accessed the association of LIG3 single nucleotide polymorphisms (SNPs) with gastric cancer risk, especially in Chinese population. The current study was undertaken to investigate contribution of LIG3 gene polymorphisms to gastric cancer risk. We first applied TaqMan assay to genotype three LIG3 gene SNPs (rs1052536 C > T, rs3744356 C > T, rs4796030 A > C) in 1142 patients with gastric cancer and 1173 healthy controls. And then, we adopted unconditional multivariate logistic regression analysis to estimate the association between LIG3 SNP genotypes and gastric cancer risk. In all, no positive association was found between the three LIG3 SNPs and gastric cancer risk in single locus analysis or combined risk genotypes analysis. However, compared with participants with rs4796030 AA genotype, participants with the AC/CC had a decreased risk of developing tumors from cardia at an adjusted OR of 0.68 (95% CI = 0.48-0.96, P = 0.026). In addition, we found that participants harboring 2-3 risk genotypes were at a significantly increased risk of developing tumor from cardia (adjusted OR = 1.63, 95% CI = 1.16-2.28, P = 0.005). These results suggest that genetic variations in LIG3 gene may play a weak role in modifying the risk of gastric cancer. Future functional studies should be performed to elucidate the biological role of LIG3 polymorphisms in gastric cancer carcinogenesis.
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Affiliation(s)
- Rui-Xi Hua
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China; Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China
| | - Zhenjian Zhuo
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Jinhong Zhu
- Department of Clinical Laboratory, Molecular Epidemiology Laboratory, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China
| | - Shao-Dan Zhang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China
| | - Wen-Qiong Xue
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China
| | - Xi-Zhao Li
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China
| | - Jing He
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
| | - Wei-Hua Jia
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China.
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Ye F, Wang H, Liu J, Cheng Q, Chen X, Chen H. Association of SMUG1 SNPs in Intron Region and Linkage Disequilibrium with Occurrence of Cervical Carcinoma and HPV Infection in Chinese Population. J Cancer 2019; 10:238-248. [PMID: 30662544 PMCID: PMC6329855 DOI: 10.7150/jca.27103] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 10/23/2018] [Indexed: 01/08/2023] Open
Abstract
Background and Aims: This study was aim to investigate the relationship between the four intron SNPs (rs3087404, rs2029167, rs2029166 and rs7296239) of SMUG1 and the susceptibility of cervical squamous cell carcinoma. Methods: Four SMUG1 intron SNPs (rs3087404, rs2029167, rs2029166 and rs7296239) were genotyped by MA-PCR in 400 CSCCs, 400 CIN III and 1200 controls. qRT-PCR and Western blot were used to detect the SMUG1 mRNA and protein expression. Results: Interestingly, we found that the homozygous GG of rs3087404 had a significantly increased risk of CIN III [OR=1.78(1.27-2.51), P= 0.001] and CSCCs [OR=4.04(2.94-5.55), P=0.000]. The individuals with G allele or G carrier (AG +GG) at rs3087404 were at higher risk for CSCCs [OR=1.34 (1.04-1.71), P= 0.022]. Similarly, the homozygous GG of rs2029167 also had an increased risk of CIN III [OR=2.56 (1.91-3.43), P= 0.000] and CSCCs [OR=4.05(3.02-5.44), P=0.000]. The individuals with G allele or G carrier (AG +GG) at rs2029167 were at higher risk for CINIII [OR=1.41(1.10-1.80), P= 0.006] and CSCCs [OR=1.91 (1.48-2.47), P= 0.000]. In HR-HPV positive group, both the homozygous GG of rs3087404 and the homozygous GG of rs2029167 had an increased risk to CIN III and CSCC. Stratified analysis of the number of sexual partners and the age of first sexual intercourse found that the rs3087404 (A/G) had a particularly high level of enrichment in the CIN III or CSCCs groups. About the rs2029167 (A/G), we only found a particularly high level of enrichment grouping by the number of sexual partners in the CIN III and CSCCs groups. Meanwhile, we also found that there is a correlation between the SNPs of SMUG1 rs3087404 (A/G) and rs2029167 (A/G) with tumor cell differentiation and family heredity. But we didn't find that there was an association between the deferent genotypes of SMUG1 rs2029166 and rs7296239 with SMUG1 gene mRNA or protein expression. During the linkage disequilibrium analysis between rs3087404 (A/G) and rs2029167 (A/G), the genotype with AA-GG [OR=3.14(1.95-5.05)], AG-GG [OR=2.45(1.58-3.89)], GG-AA [OR=2.24(1.28-3.90)] and GG-AG [OR=2.58(1.54-4.32)] significantly increased the risk of CIN III. More notably, this risk is much greater in CSCCs: AA-GG [OR=7.13(4.03-12.61)], AG-GG [OR=7.22(4.21-12.38)], GG-AA [OR=8.60(4.73-15.63)], GG-AG [OR=9.64(5.43-17.13)]. Additionally, most GG (rs3087404) genotypes were linkage GG-AG (44/77, 80/140) in the CIN III and CSCCs, while most GG (rs2029167) genotypes were linkage genotype AG-GG (79/145, 112/184) in the CIN III and CSCCs, respectively. Conclusions: These findings suggested that there was association between the two genetic polymorphisms of SMUG1 rs3087404(A/G) and rs2029167(A/G) with the susceptibility of CIN III and CSCCs, and there was a linkage disequilibrium between the rs3087404 with the rs2029167 in CIN III and CSCCs. This particular linkage disequilibrium can be used as predictive biomarkers of CIN III and CSCC.
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Affiliation(s)
- Feng Ye
- Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, P.R. China
| | - Hanzhi Wang
- Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, P.R. China
| | - Jia Liu
- Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, P.R. China
| | - Qi Cheng
- Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, P.R. China
| | - Xiaojing Chen
- Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, P.R. China
| | - Huaizeng Chen
- Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, P.R. China
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15
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Kang SW, Kim SK, Park HJ, Chung JH, Ban JY. Human 8-oxoguanine DNA glycosylase gene polymorphism (Ser326Cys) and cancer risk: updated meta-analysis. Oncotarget 2018; 8:44761-44775. [PMID: 28415770 PMCID: PMC5546516 DOI: 10.18632/oncotarget.16226] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 03/03/2017] [Indexed: 01/30/2023] Open
Abstract
Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) has been reported to have a relationship with the risk of the development of various cancers. Many studies have described the influence of Ser326Cys polymorphism of the hOGG1 gene on cancer susceptibility. However, the results have remained inconclusive and controversial. Therefore, we performed a meta-analysis to more precisely determine the relationship between the hOGG1 polymorphism and the development of cancer.Electronic databases including PubMed, Embase, Google Scholar, and the Korean Studies Information Service System (KISS) were searched. The odds ratio (OR), 95% confidence interval (CI), and p value were calculated to assess the strength of the association with the risk of cancer using Comprehensive Meta-analysis software (Corporation, NJ, USA). The 127 studies including 38,757 cancer patients and 50,177 control subjects were analyzed for the meta-analysis.Our meta-analysis revealed that G allele of Ser326Cys polymorphism of the hOGG1 gene statistically increased the susceptibility of cancer (all population, OR = 1.092, 95% CI = 1.051-1.134, p < 0.001; in Asian, OR = 1.095, 95% CI = 1.048-1.145, p < 0.001; in Caucasian, OR = 1.097, 95% CI = 1.033-1.179, p = 0.002). Also, other genotype models showed significant association with cancer (p < 0.05, respectively).The present meta-analysis concluded that the G allele was associated with an increased risk of cancer. It suggested that the hOGG1 polymorphism may be a candidate marker of cancer.
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Affiliation(s)
- Sang Wook Kang
- Department of Dental Pharmacology, School of Dentistry, Dankook University, Cheonan, Republic of Korea
| | - Su Kang Kim
- Kohwang Medical Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Hae Jeong Park
- Kohwang Medical Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Joo-Ho Chung
- Kohwang Medical Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Ju Yeon Ban
- Department of Dental Pharmacology, School of Dentistry, Dankook University, Cheonan, Republic of Korea
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16
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Qiao L, Feng X, Wang G, Zhou B, Yang Y, Li M. Polymorphisms in BER genes and risk of breast cancer: evidences from 69 studies with 33760 cases and 33252 controls. Oncotarget 2018; 9:16220-16233. [PMID: 29662639 PMCID: PMC5882330 DOI: 10.18632/oncotarget.23804] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
Recently, numerous studies have reported an association between single nucleotide polymorphisms in base-excision repair genes and the risk of developing breast cancer, however there is no consensus. The aim of this meta-analysis was to review and quantitatively assess the relationship between single nucleotide polymorphisms in base-excision repair genes and breast cancer risk. The results suggested that a mutation of T to G in rs1760944 may lead to a higher risk of developing breast cancer in the Mongoloid population, and G to A of rs25487 significantly reduced the risk of breast cancer in Mongoloid and Caucasoid populations. In contrast to the CC and CG genotypes, the GG genotype of rs1052133 located on theOGG1 gene appeared to be a protective factor against developing breast cancer in both Mongoloid and Caucasoid populations. There was no evidence to suggest that rs25489, rs1799782, rs1130409, rs1805414 and rs1136410 were associated with breast cancer risk. In conclusion, this study provides evidence to support the theory that DNA repair genes are associated with breast cancer risk, providing information to further understand breast cancer etiology. and The potential biological pathways linking DNA repair, ethnic background, environment and breast cancer require further investigation.
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Affiliation(s)
- Lele Qiao
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Xiaoshan Feng
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Gongping Wang
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Bo Zhou
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Yantong Yang
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Mengxiang Li
- Henan University of Science and Technology, LuoYang, Henan, 471023, China
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17
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Liao YH, Ren JT, Zhang W, Zhang ZZ, Lin Y, Su FX, Jia WH, Tang LY, Ren ZF. Polymorphisms in homologous recombination repair genes and the risk and survival of breast cancer. J Gene Med 2017; 19. [PMID: 28940489 DOI: 10.1002/jgm.2988] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Revised: 08/23/2017] [Accepted: 09/13/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Immunoglobulin (Ig)A antibody of Epstein-Barr virus (EBV) was found to associate with breast cancer (BC), whereas IgA positivity was related to a series of genetic markers in the genes of homologous recombination repair system (HRRs). We assessed the associations of the polymorphisms in HRR genes with the risk and survival of BC. METHODS A case-control study was conducted with 1551 bc cases and 1605 age-matched healthy controls between October 2008 and March 2012 in the Guangzhou Breast Cancer Study (GZBCS), China, and the case population were followed up until 31 January 2016. Five single nucleotide polymorphisms of candidate genes in HRR system were genotyped. Odds ratios (ORs) and hazards ratios (HRs) were calculated using multivariate logistic regression and Cox proportional hazards regression to estimate the risk and prognostic effect, respectively. RESULTS RFC1 rs6829064 (AA) was associated with an increased BC risk [OR = 1.35; 95% confidence interval (CI) = 1.06-1.73] compared to the wild genotype (GG). NRM rs1075496 (GT/TT versus GG) was associated with a worse progression-free survival (PFS) and the HR was 1.34 (95% CI = 1.01-1.78), particularly among advanced patients. LIG3 rs1052536 (CT/TT versus CC) was associated with a better PFS and the HR was 0.70 (95% CI = 0.53-0.93). However, RAD54L rs1710286 and RPA1 rs11078676 were not observed to be associated with either the risk or survival of BC. CONCLUSIONS The findings of the present study suggest that the polymorphisms in HRR genes were associated with BC risk (RFC1 rs6829064) and prognosis (NRM rs1075496 and LIG3 rs1052536), whereas RAD54L rs1710286 and RPA1 rs11078676 had null associations with BC.
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Affiliation(s)
- Yu-Huang Liao
- The School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Jun-Ting Ren
- The School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Wei Zhang
- The School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zheng-Zheng Zhang
- The School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Ying Lin
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Feng-Xi Su
- The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wei-Hua Jia
- The Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Lu-Ying Tang
- The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ze-Fang Ren
- The School of Public Health, Sun Yat-sen University, Guangzhou, China
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18
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Sanjari Moghaddam A, Nazarzadeh M, Bidel Z, Karamatinia A, Darvish H, Mosavi Jarrahi A. hOGG1 gene polymorphism and breast cancer risk: A systematic review and meta-analysis study. Breast J 2017; 24:70-73. [PMID: 28608470 DOI: 10.1111/tbj.12842] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
To address the effect of hGGO1 (rs1052133) gene polymorphism on the risk of breast cancer, a meta-analysis was performed. We pooled adjusted odds ratios (OR) as overall and three subgroups (menopausal status, ethnicity, and study setting). In overall analysis, we found a significant association when the model of inheritance was homozygote (pooled OR 1.14; 95% CI 1.01, 1.29). Subgroup analysis showed significant association for homozygote genetic models among postmenopause women (OR 1.23; 95% CI 1.01, 1.49) and Asian population (OR 1.17; 95% CI 1.01, 1.35). This study suggested that the carrier of Ser326Cys polymorphism of hOGG1, Cys/Cys vs Ser/Ser, are at higher risk for breast cancer, independent of other hormonal and environmental risk factors.
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Affiliation(s)
| | - Milad Nazarzadeh
- The Collaboration Center of Meta-Analysis Research (ccMETA), Iranian Research Center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Zeinab Bidel
- The Collaboration Center of Meta-Analysis Research (ccMETA), Iranian Research Center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Aliasghar Karamatinia
- Department of Social Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Darvish
- Department of Genetic, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Mosavi Jarrahi
- Department of Social Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
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19
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Ren Y, Lai Y, Laverde EE, Lei R, Rein HL, Liu Y. Modulation of trinucleotide repeat instability by DNA polymerase β polymorphic variant R137Q. PLoS One 2017; 12:e0177299. [PMID: 28475635 PMCID: PMC5419657 DOI: 10.1371/journal.pone.0177299] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 04/25/2017] [Indexed: 12/13/2022] Open
Abstract
Trinucleotide repeat (TNR) instability is associated with human neurodegenerative diseases and cancer. Recent studies have pointed out that DNA base excision repair (BER) mediated by DNA polymerase β (pol β) plays a crucial role in governing somatic TNR instability in a damage-location dependent manner. It has been shown that the activities and function of BER enzymes and cofactors can be modulated by their polymorphic variations. This could alter the function of BER in regulating TNR instability. However, the roles of BER polymorphism in modulating TNR instability remain to be elucidated. A previous study has shown that a pol β polymorphic variant, polβR137Q is associated with cancer due to its impaired polymerase activity and its deficiency in interacting with a BER cofactor, proliferating cell nuclear antigen (PCNA). In this study, we have studied the effect of the pol βR137Q variant on TNR instability. We showed that pol βR137Q exhibited weak DNA synthesis activity to cause TNR deletion during BER. We demonstrated that similar to wild-type pol β, the weak DNA synthesis activity of pol βR137Q allowed it to skip over a small loop formed on the template strand, thereby facilitating TNR deletion during BER. Our results further suggest that carriers with pol βR137Q polymorphic variant may not exhibit an elevated risk of developing human diseases that are associated with TNR instability.
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Affiliation(s)
- Yaou Ren
- Biochemistry Ph.D. Program, Florida International University, Miami, Florida, United States of America
| | - Yanhao Lai
- Department of Chemistry and Biochemistry, Florida International University, Miami, Florida, United States of America
| | - Eduardo E. Laverde
- Biochemistry Ph.D. Program, Florida International University, Miami, Florida, United States of America
| | - Ruipeng Lei
- Biochemistry Ph.D. Program, Florida International University, Miami, Florida, United States of America
| | - Hayley L. Rein
- Department of Chemistry and Biochemistry, Florida International University, Miami, Florida, United States of America
| | - Yuan Liu
- Biochemistry Ph.D. Program, Florida International University, Miami, Florida, United States of America
- Department of Chemistry and Biochemistry, Florida International University, Miami, Florida, United States of America
- Biomolecular Sciences Institute, Florida International University, Miami, Florida, United States of America
- * E-mail:
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20
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Azevedo AP, Silva SN, De Lima JP, Reichert A, Lima F, Júnior E, Rueff J. DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: The role of base excision repair genes polymorphisms. Oncol Lett 2017; 13:4641-4650. [PMID: 28599464 PMCID: PMC5452988 DOI: 10.3892/ol.2017.6065] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 01/26/2017] [Indexed: 02/06/2023] Open
Abstract
The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single-nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2-positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN-MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility.
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Affiliation(s)
- Ana P Azevedo
- Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculty of Medical Sciences, NOVA University of Lisbon, 1169-056 Lisbon, Portugal.,Department of Clinical Pathology, Hospital of São Francisco Xavier, West Lisbon Hospital Centre, 1449-005 Lisbon, Portugal
| | - Susana N Silva
- Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculty of Medical Sciences, NOVA University of Lisbon, 1169-056 Lisbon, Portugal
| | - João P De Lima
- Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculty of Medical Sciences, NOVA University of Lisbon, 1169-056 Lisbon, Portugal
| | - Alice Reichert
- Department of Clinical Haematology, Hospital of São Francisco Xavier, West Lisbon Hospital Centre, 1449-005 Lisbon, Portugal
| | - Fernando Lima
- Department of Clinical Haematology, Hospital of São Francisco Xavier, West Lisbon Hospital Centre, 1449-005 Lisbon, Portugal
| | - Esmeraldina Júnior
- Department of Clinical Pathology, Hospital of São Francisco Xavier, West Lisbon Hospital Centre, 1449-005 Lisbon, Portugal
| | - José Rueff
- Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculty of Medical Sciences, NOVA University of Lisbon, 1169-056 Lisbon, Portugal
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21
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Modulation of Colorectal Cancer Risk by Polymorphisms in 51Gln/His, 64Ile/Val, and 148Asp/Glu of APEX Gene; 23Gly/Ala of XPA Gene; and 689Ser/Arg of ERCC4 Gene. Gastroenterol Res Pract 2017; 2017:3840243. [PMID: 28386271 PMCID: PMC5366231 DOI: 10.1155/2017/3840243] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 12/01/2016] [Accepted: 12/07/2016] [Indexed: 12/14/2022] Open
Abstract
Polymorphisms in DNA repair genes may affect the activity of the BER (base excision repair) and NER (nucleotide excision repair) systems. Using DNA isolated from blood taken from patients (n = 312) and a control group (n = 320) with CRC, we have analyzed the polymorphisms of selected DNA repair genes and we have demonstrated that genotypes 51Gln/His and 148Asp/Glu of APEX gene and 23Gly/Ala of XPA gene may increase the risk of colorectal cancer. At the same time analyzing the gene-gene interactions, we suggest the thesis that the main factor to be considered when analyzing the impact of polymorphisms on the risk of malignant transformation should be intergenic interactions. Moreover, we are suggesting that some polymorphisms may have impact not only on the malignant transformation but also on the stage of the tumor.
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22
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Kamali M, Kargar S, Heiranizadeh N, Zare M, Kargar S, Zare Shehneh M, Neamatzadeh H. Lack of any Association between the Hogg1 Ser326Cys Polymorphism and Breast Cancer Risk: a Systematic Review And Meta-Analysis Of 18 Studies. Asian Pac J Cancer Prev 2017; 18:245-251. [PMID: 28240527 PMCID: PMC5563108 DOI: 10.22034/apjcp.2017.18.1.245] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background: The human 8-oxoguanine DNA glycosylase (hOGG1) gene may be linked with cancer susceptibility. The aim of this study was to quantitatively summarize any association between the hOGG1 Ser326Cys polymorphism and breast cancer (BC) risk. Materials and Methods: A comprehensive search of the PubMed, Embase, and ISI web of knowledge databases for papers published before 1 October 2016 was conducted. Summary odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were estimated, with fixed-effects or random-effects models when appropriate, to assess any association. Results: A total of 9,434 cases and 10,497 controls from 18 studies were included in this meta-analysis. When the eligible studies were pooled, there was no evidence found for a significant association between the hOGG1 Ser326Cys polymorphism and BC in in all genetic contrast models G vs. C (OR=1.19, 95% CI 0.92– 1.53), CG vs. CC (OR = 0.97, 95% CI 0.91-1.04, p = 0.46), GG vs. CC (OR = 1.11, 95% CI 0.91-1.35, p = 0.30), GG + CG vs. CC (OR = 0.98, 95% CI 0.92-1.05, p = 0.67), and GG vs. CG + CC (OR = 1.22, 95% CI 0.98-1.52, p = 0.07). According to subgroup analysis, we also did not find a significant association between the hOGG1 Ser326Cys polymorphism and BC risk in Asians and Caucasians considered separately. Conclusions: The current meta-analysis suggests that the hOGG1 Ser326Cys polymorphism is not significantly associated with BC risk.
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Affiliation(s)
- Mahdieh Kamali
- Department of Perinatology, School of Medicine, Tehran University Medical of Sciences, Tehran.
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23
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Romanowicz H, Pyziak Ł, Jabłoński F, Bryś M, Forma E, Smolarz B. Analysis of DNA Repair Genes Polymorphisms in Breast Cancer. Pathol Oncol Res 2016; 23:117-123. [PMID: 27571987 DOI: 10.1007/s12253-016-0110-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Accepted: 08/24/2016] [Indexed: 10/21/2022]
Abstract
Genetic polymorphisms in the DNA repair genes may be associated with increased cancer risk. The purpose of this study was to evaluate the association of the DNA repair genes polymorphisms with the risk of breast cancer development. The study included 200 breast cancer patients and 200 healthy controls. The following polymorphisms were studied: C/G (Ser326Cys, rs1052133) of the hOGG1, A/C (IVS5 + 33, rs3212961) of the ERCC1, A/C (Lys939Gln, rs2228001) of the XPC, C/T (Thr241Met, rs861539) of the XRCC3, G/T (Leu787Leu, rs1800392) of the WRN and G/T (Ser307Ser, rs1056503) of the XRCC4 gene. Presented study showed statistically significant increase in the breast cancer development risk of the G/G hOGG1 genotype (OR 8.13; 95 % CI, 4.37-15.14; p < 0.001) and for the G hOGG1 allele (OR 5.11; 95 % CI, 3.69-7.06; p < 0.001), as well as for the C/C ERCC1 genotype (OR 10.61; 95 % CI, 5.72-19.69; p < 0.001) and the C ERCC1 allele (OR 4.66; 95 % CI, 3.43-6.34; p < 0.001) in patients with breast cancer in comparison with healthy control group. We also observed positive association of the C/C XPC genotype (OR 3.80; 95 % CI, 2.27-6.38; p < 0.001) as well as the C XPC allele occurrence with an increased breast cancer development risk (OR 2.65; 95 % CI, 1.98-3.55; p < 0.001). Furthermore, we found an association of the G/T WRN gene polymorphism with increased risk of carcinoma. The hOGG1, ERCC1, XPC and WRN genes polymorphisms may be related to development of breast cancer.
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Affiliation(s)
- Hanna Romanowicz
- Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Rzgowska 281/289, 93-338, Lodz, Poland.
| | - Łukasz Pyziak
- Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Rzgowska 281/289, 93-338, Lodz, Poland
| | - Filip Jabłoński
- Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Rzgowska 281/289, 93-338, Lodz, Poland
| | - Magdalena Bryś
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237, Lodz, Poland
| | - Ewa Forma
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237, Lodz, Poland
| | - Beata Smolarz
- Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Rzgowska 281/289, 93-338, Lodz, Poland
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Sanjari Moghaddam A, Nazarzadeh M, Noroozi R, Darvish H, Mosavi Jarrahi A. XRCC1 and OGG1 Gene Polymorphisms and Breast Cancer: A Systematic Review of Literature. IRANIAN JOURNAL OF CANCER PREVENTION 2016; 9:e3467. [PMID: 27366307 PMCID: PMC4922200 DOI: 10.17795/ijcp-3467] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 08/31/2015] [Accepted: 11/09/2015] [Indexed: 12/18/2022]
Abstract
Context: Known polymorphisms of DNA repair genes can be associated with the risk of many types of cancer. There is no consensus regarding association between XRCC1 and OGG1 with breast cancer (BC). Objectives: The aim of this study is to collect relevant published studies systematically. Data Sources: Sixty-two publications were identified through searching PubMed, PubMed Central, ISI web of knowledge, and reference list of related articles. Study Selection: We performed a systematic review according MOOSE guideline criteria. All longitudinal cohort and case-control studies investigating association of any type and grade of breast cancer with XRCC1 and OGG1 gene and their polymorphisms were eligible for initial inclusion. Data Extraction: Two authors screened titles and abstracts and extracted all needed information from eligible studies. Four research methodological components causing bias for the association between gene polymorphisms and breast cancer risk, including source of controls sampling, population ethnicity, sample size of studies and menopausal status of cases and controls was used for assessment of quality of studies Results: A total of 14,793 breast cancer cases and 15,409 controls were included in assessment of XRCC1 Arg194Trp. Four studies showed significant association and one study showed protective effect of XRCC1 Arg194Trp and BC. A total of 7,716 cases and 7,370 controls were included for XRCC1 Arg280His. Only one study showed significant association of XRCC1 Arg280His and breast cancer (OR = 1.82 (1.06 - 3.15). A total of 27,167 cases and 31,998 controls were included to estimate association between XRCC1 Arg399Gln polymorphism and breast cancer. Seven studies showed significant association and one showed protective effect of XRCC1 Arg399Gln and BC. A total of 9,417 cases and 11,087 controls were included for OGG1 Ser326Cys. Among studies focused on OGG1 Ser326Cys, none showed significant association with breast cancer. Conclusions: Systematic search of major databases identify many studies addressing the relationship between BC and susceptible alleles in the base excision repair genes and the fact that there are many variations in the magnitude of association depending on inheritance model and the population of the study.
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Affiliation(s)
| | - Milad Nazarzadeh
- Iranian Research Center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, IR Iran
| | - Rezvan Noroozi
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Hossein Darvish
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Alireza Mosavi Jarrahi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran; Iranian Research Center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, IR Iran; Faculty of Health Sciences, Simon Fraser University, BC., Canada
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25
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Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2016:3125989. [PMID: 26649135 PMCID: PMC4663340 DOI: 10.1155/2016/3125989] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 07/08/2015] [Accepted: 07/27/2015] [Indexed: 12/12/2022]
Abstract
DNA oxidative lesions are widely considered as a potential risk factor for colorectal cancer development. The aim of this work was to determine the role of the efficiency of base excision repair, both in lymphocytes and in epithelial tissue, in patients with CRC and healthy subjects. SNPs were identified within genes responsible for steps following glycosylase action in BER, and patients and healthy subjects were genotyped. A radioisotopic BER assay was used for assessing repair efficiency and TaqMan for genotyping. Decreased BER activity was observed in lymphocyte extract from CRC patients and in cancer tissue extract, compared to healthy subjects. In addition, polymorphisms of EXO1, LIG3, and PolB may modulate the risk of colorectal cancer by decreasing (PolB) or increasing (LIG3 and EXO1) the chance of malignant transformation.
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26
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Ali K, Mahjabeen I, Sabir M, Baig RM, Zafeer M, Faheem M, Kayani MA. Germline variations of apurinic/apyrimidinic endonuclease 1 (APEX1) detected in female breast cancer patients. Asian Pac J Cancer Prev 2015; 15:7589-95. [PMID: 25292033 DOI: 10.7314/apjcp.2014.15.18.7589] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Apurinic/apyrimidinic endonuclease 1 (APEX1) is a multifunctional protein which plays a central role in the BER pathway. APEX1 gene being highly polymorphic in cancer patients and has been indicated to have a contributive role in Apurinic/apyrimidinic (AP) site accumulation in DNA and consequently an increased risk of cancer development. In this case-control study, all exons of the APEX1 gene and its exon/intron boundaries were amplified in 530 breast cancer patients and 395 matched healthy controls and then analyzed by single-stranded conformational polymorphism followed by sequencing. Sequence analysis revealed fourteen heterozygous mutations, seven 5'UTR, one 3 'UTR, two intronic and four missense. Among identified mutations one 5'UTR (rs41561214), one 3'UTR (rs17112002) and one missense mutation (Ser129Arg, Mahjabeen et al., 2013) had already been reported while the remaining eleven mutations. Six novel mutations (g.20923366T>G, g.20923435G>A, g.20923462G>A, g.20923516G>A, 20923539G>A, g.20923529C>T) were observed in 5'UTR region, two (g.20923585T>G, g.20923589T>G) in intron1 and three missense (Glu101Lys, Ala121Pro, Ser123Trp) in exon 4. Frequencues of 5'UTR mutations; g.20923366T>G, g.20923435G>A and 3'UTR (rs17112002) werecalculated as 0.13, 0.1 and 0.1 respectively. Whereas, the frequency of missense mutations Glu101Lys, Ser123Trp and Ser129Arg was calculated as 0.05. A significant association was observed between APEX1 mutations and increased breast cancer by ~9 fold (OR=8.68, 95%CI=2.64 to 28.5) with g.20923435G>A (5'UTR) , ~13 fold (OR= 12.6, 95%CI=3.01 to 53.0) with g.20923539G>A (5'UTR) and~5 fold increase with three missense mutations [Glu101Lys (OR=4.82, 95%CI=1.97 to 11.80), Ser123Trp (OR=4.62, 95%CI=1.7 to 12.19), Ser129Arg (OR=4.86, 95%CI=1.43 to 16.53)]. The incidence of observed mutations was found higher in patients with family history and with early menopause. In conclusion, our study demonstrates a significant association between germ line APEX1 mutations and breast cancer patients in the Pakistani population.
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Affiliation(s)
- Kashif Ali
- Department of Biosciences, COMSATS Institute of Information and Technology, Islamabad, Pakistan E-mail :
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27
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Ali K, Mahjabeen I, Sabir M, Mehmood H, Kayani MA. OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data. DISEASE MARKERS 2015; 2015:690878. [PMID: 26089588 PMCID: PMC4452349 DOI: 10.1155/2015/690878] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 04/09/2015] [Indexed: 01/10/2023]
Abstract
In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3'UTR mutations, three missense mutations, and a nonsense mutation. Significantly (p < 0.001) increased (~29 fold) breast cancer risk was associated with a splice site variant g.9800972T>G and 3'UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold) increase in breast cancer risk was associated with g.9793680G>A (p < 0.009). Similarly ~14-fold increased risk was associated with Val159Gly (p < 0.01), ~17-fold with Gly221Arg (p < 0.005), and ~18-fold with Ser326Cys (p < 0.004) in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold (p < 0.01) increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer.
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Affiliation(s)
- Kashif Ali
- Cancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan
| | - Ishrat Mahjabeen
- Cancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan
| | - Maimoona Sabir
- Cancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan
| | - Humera Mehmood
- Nuclear Medicine Oncology & Radiotherapy Institute (NORI), Islamabad 44000, Pakistan
| | - Mahmood Akhtar Kayani
- Cancer Genetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan
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28
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Mi J, Tian G, Liu S, Li X, Ni T, Zhang L, Wang B. The relationship between altered mitochondrial DNA copy number and cancer risk: a meta-analysis. Sci Rep 2015; 5:10039. [PMID: 25952580 PMCID: PMC4424798 DOI: 10.1038/srep10039] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 03/24/2015] [Indexed: 12/30/2022] Open
Abstract
Currently, a comprehensive assessment between mitochondrial DNA (mtDNA) content and cancer risk is lacking. We designed this meta-analysis to test the hypothesis that altered mtDNA copy number might influence genetic susceptibility to some specific types of cancer. The processes of literature search, eligibility appraisal and data retrieval were independently completed in duplicate. The mtDNA copy number which was dichotomized or classified into tertiles was compared between cancer cases and controls. Twenty-six articles with 38 study groups were analyzed among 6682 cases and 9923 controls. When dichotomizing mtDNA copy number at the median value, there was an 11% increased cancer risk for carriers of high mtDNA content (P = 0.320). By cancer type, high mtDNA content was associated with an increased risk for lymphoma (OR = 1.76; P = 0.023) but a reduced risk for skeleton cancer (OR = 0.39; P = 0.001). Carriers of the 2nd and 3rd tertiles of mtDNA copy number had an 1.74-fold (P = 0.010) and 2.07-fold (P = 0.021) increased risk of lymphoma, respectively. By contrast, there was correspondingly a 56% (P < 0.001) and 80% (P < 0.001) reduced risk of skeleton cancer. Our findings suggested that elevated mtDNA content was associated with a higher risk for lymphoma, but a lower risk for skeleton cancer.
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Affiliation(s)
- Jia Mi
- Medicine and Pharmacy Research Center
| | - Geng Tian
- Medicine and Pharmacy Research Center
| | | | | | | | | | - Bin Wang
- Institute of Molecular Imaging, Binzhou Medical University, Yantai, Shandong, China
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Thakur S, Dhiman M, Tell G, Mantha AK. A review on protein-protein interaction network of APE1/Ref-1 and its associated biological functions. Cell Biochem Funct 2015; 33:101-12. [DOI: 10.1002/cbf.3100] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 02/10/2015] [Accepted: 02/24/2015] [Indexed: 12/17/2022]
Affiliation(s)
- S. Thakur
- Center for Biosciences, School of Basic and Applied Sciences; Central University of Punjab; Bathinda Punjab India
| | - M. Dhiman
- Center for Genetic Diseases and Molecular Medicine, School of Emerging Life Science Technologies; Central University of Punjab; Bathinda Punjab India
| | - G. Tell
- Department of Medical and Biological Sciences; University of Udine; Udine Italy
| | - A. K. Mantha
- Center for Biosciences, School of Basic and Applied Sciences; Central University of Punjab; Bathinda Punjab India
- Department of Biochemistry and Molecular Biology; University of Texas Medical Branch; Galveston TX USA
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30
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Macías-Gómez NM, Peralta-Leal V, Meza-Espinoza JP, Gutiérrez-Angulo M, Durán-González J, Ramírez-González JM, Gaspar-Del Toro A, Norberto-Rodríguez A, Leal-Ugarte E. Polymorphisms of the XRCC1 gene and breast cancer risk in the Mexican population. Fam Cancer 2015; 14:349-54. [DOI: 10.1007/s10689-015-9787-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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31
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A systematic review and meta-analysis of the association between OGG1 Ser326Cys polymorphism and cancers. Med Oncol 2015; 32:472. [DOI: 10.1007/s12032-014-0472-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 12/18/2014] [Indexed: 12/26/2022]
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32
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Xie H, Gong Y, Dai J, Wu X, Gu J. Genetic variations in base excision repair pathway and risk of bladder cancer: a case-control study in the United States. Mol Carcinog 2015; 54:50-7. [PMID: 24038406 DOI: 10.1002/mc.22073] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2013] [Revised: 06/17/2013] [Accepted: 07/01/2013] [Indexed: 02/03/2023]
Abstract
Base excision repair (BER) is one of the major cellular DNA repair pathways that repairs small isolated foci of DNA damage including reduced or oxidized single bases or fragments and small, non-bulky adducts. Genetic variations in BER genes may affect DNA repair capacity and increase susceptibility to bladder cancer. In a case-control study of 801 bladder cancer patients and 801 matched controls, we evaluated the associations of 167 single nucleotide polymorphisms (SNPs) from 19 genes of the BER pathway with the risk of bladder cancer. In individual SNP analysis, 13 SNPs in 10 BER pathway genes were significantly associated with bladder cancer risk. The most significant SNP was rs2029167 in the SMUG1 gene. The homozygous variant GG genotype was associated with a 1.42-fold increased risk of bladder cancer (95% confidence interval [CI], 1.11-1.82, P=0.005). Cumulative effect analysis showed joint effects of increased risk of bladder cancer with increasing number of unfavorable genotypes in patients. Classification and regression tree analysis further revealed high-order gene-gene interactions and categorized the study subjects into low-, medium-low-, medium-high-, and high-risk groups. Compared with the low-risk group, the odds ratio for medium-low-, medium-high-, and high-risk group was 1.83 (95% CI: 1.23-2.72), 2.61 (95% CI: 1.79-3.80), and 3.05 (95% CI: 2.08-4.46), respectively (P for trend<0.001). Our results suggest that genetic variations in BER pathway genes modulate the risk of bladder cancer individually and jointly.
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Affiliation(s)
- Hui Xie
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas; State Key Laboratory of Reproductive Medicine, Department of Breast Surgery, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China
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33
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Boesaard EP, Vogelaar IP, Bult P, Wauters CA, van Krieken JHJ, Ligtenberg MJ, van der Post RS, Hoogerbrugge N. Germline MUTYH gene mutations are not frequently found in unselected patients with papillary breast carcinoma. Hered Cancer Clin Pract 2014; 12:21. [PMID: 25937855 PMCID: PMC4416291 DOI: 10.1186/1897-4287-12-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Accepted: 11/26/2014] [Indexed: 11/17/2022] Open
Abstract
MUTYH-associated polyposis (MAP) is an autosomal recessive disease, which predisposes to polyposis and colorectal cancer. There is a trend towards an increased risk of breast cancer in MAP patients, with a remarkable proportion of papillary breast cancers. To determine whether MUTYH mutations are associated with this specific and rare type of breast cancer, 53 unselected patients with papillary breast cancer were analyzed for founder mutations in the MUTYH gene. No germline mutations were identified, indicating that biallelic MUTYH mutations are not a frequent underlying cause for the development of papillary carcinomas of the breast.
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Affiliation(s)
- Ewout P Boesaard
- Department of Human Genetics, Radboud university medical center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Ingrid P Vogelaar
- Department of Human Genetics, Radboud university medical center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Peter Bult
- Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands
| | - Carla Ap Wauters
- Department of Pathology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - J Han Jm van Krieken
- Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands
| | - Marjolijn Jl Ligtenberg
- Department of Human Genetics, Radboud university medical center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands ; Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands
| | - Rachel S van der Post
- Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands
| | - Nicoline Hoogerbrugge
- Department of Human Genetics, Radboud university medical center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
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Xie SH, Yu ITS, Tse LA, Au JSK, Wang F, Lau JSM, Zhang B. Domestic incense burning and nasopharyngeal carcinoma: a case-control study in Hong Kong Chinese. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2014; 55:751-756. [PMID: 25124928 DOI: 10.1002/em.21894] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Accepted: 07/29/2014] [Indexed: 06/03/2023]
Abstract
Incense burning is a powerful producer of carcinogens and has been considered as a risk factor for nasopharyngeal carcinoma (NPC). We conducted a case-control study and case-only analyses to investigate the effect of incense burning and its interaction with genetic background on NPC risk among Hong Kong Chinese. Between June 2010 and December 2012, we recruited 352 incident cases of NPC and 410 controls. We collected information on lifelong practice of domestic incense burning via interviews and genotyped 80 single nucleotide polymorphisms (SNPs) in DNA repair genes. We observed an increased NPC risk associated with daily burning in women [Adjusted OR = 2.49, 95% confidence interval (CI): 1.33, 4.66] but not in men. The adjusted OR for daily burning with poor ventilation was 2.08 (95% CI: 1.02, 4.24), while that with good ventilation was 1.35 (95% CI: 0.92, 1.98). Interactions between 2 SNPs (rs2074517 and rs4771436) and incense burning were significantly associated with NPC risk and tended to have a SNP exposure-response effect. Evidence for gene-environment interactions supported the knowledge that NPC is a multi-factorial disease resulting from the joint effects of environmental exposures and inherited susceptibility.
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Affiliation(s)
- Shao-Hua Xie
- Division of Occupational and Environmental Health, Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China
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Oxidatively induced DNA damage and its repair in cancer. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2014; 763:212-45. [PMID: 25795122 DOI: 10.1016/j.mrrev.2014.11.002] [Citation(s) in RCA: 191] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 11/03/2014] [Accepted: 11/04/2014] [Indexed: 12/28/2022]
Abstract
Oxidatively induced DNA damage is caused in living organisms by endogenous and exogenous reactive species. DNA lesions resulting from this type of damage are mutagenic and cytotoxic and, if not repaired, can cause genetic instability that may lead to disease processes including carcinogenesis. Living organisms possess DNA repair mechanisms that include a variety of pathways to repair multiple DNA lesions. Mutations and polymorphisms also occur in DNA repair genes adversely affecting DNA repair systems. Cancer tissues overexpress DNA repair proteins and thus develop greater DNA repair capacity than normal tissues. Increased DNA repair in tumors that removes DNA lesions before they become toxic is a major mechanism for development of resistance to therapy, affecting patient survival. Accumulated evidence suggests that DNA repair capacity may be a predictive biomarker for patient response to therapy. Thus, knowledge of DNA protein expressions in normal and cancerous tissues may help predict and guide development of treatments and yield the best therapeutic response. DNA repair proteins constitute targets for inhibitors to overcome the resistance of tumors to therapy. Inhibitors of DNA repair for combination therapy or as single agents for monotherapy may help selectively kill tumors, potentially leading to personalized therapy. Numerous inhibitors have been developed and are being tested in clinical trials. The efficacy of some inhibitors in therapy has been demonstrated in patients. Further development of inhibitors of DNA repair proteins is globally underway to help eradicate cancer.
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Luo H, Li Z, Qing Y, Zhang SH, Peng Y, Li Q, Wang D. Single nucleotide polymorphisms of DNA base-excision repair genes (APE1, OGG1 and XRCC1) associated with breast cancer risk in a Chinese population. Asian Pac J Cancer Prev 2014; 15:1133-40. [PMID: 24606430 DOI: 10.7314/apjcp.2014.15.3.1133] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementing group 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194 patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms (SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their association with breast cancer risk using multivariate logistic regression models. We found that XRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1 Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a high BMI (≥ 24 kg/m2). The OGG1 Cys allele provided a significant protective effect against developing cancer in women with a low BMI (< 24 kg/m2). When analyzing the combined effects of these alleles on the risk of breast cancer, we found that individuals with ≥ 2 adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser) were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinese women with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects of polymorphisms of BER genes may contribute to tumorigenesis.
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Affiliation(s)
- Hao Luo
- Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China E-mail :
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Feng YZ, Liu YL, He XF, Wei W, Shen XL, Xie DL. Association between the XRCC1 Arg194Trp polymorphism and risk of cancer: evidence from 201 case-control studies. Tumour Biol 2014; 35:10677-97. [PMID: 25064613 DOI: 10.1007/s13277-014-2326-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Accepted: 07/07/2014] [Indexed: 12/11/2022] Open
Abstract
The Arg194Trp polymorphism in the X-ray cross-complementing group 1 (XRCC1) had been implicated in cancer susceptibility. The previous published data on the association between XRCC1 Arg194Trp polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC1 Arg194Trp (59,227 cases and 81,587 controls from 201 studies) polymorphism in different inheritance models. We used odds ratios with 95 % confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was found (recessive model: (odds ration [OR] = 1.18, 95% confidence interval [CI] = 1.09-1.27; homozygous model: OR = 1.21, 95% CI = 1.10-1.33; additive model: OR = 1.05, 95% CI = 1.01-1.09) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased glioma risk was found among Asians, significantly decreased lung cancer risk was found among Caucasians, and significant increased breast cancer risk was found among hospital-based studies. In summary, this meta-analysis suggests that Arg194Trp polymorphism may be associated with increased breast cancer risk, Arg194Trp polymorphism is associated with increased glioma risk among Asians, and Arg194Trp polymorphism is associated with decreased lung cancer risk among Caucasians. In addition, our work also points out the importance of new studies for Arg194Trp association in some cancer types, such as gastric, pancreatic, prostate, and nasopharyngeal cancers, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC1 Arg194Trp polymorphism in cancer development (I (2) > 75%).
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Affiliation(s)
- Yan-Zhong Feng
- Department of maternity, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China
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Lee E, Levine EA, Franco VI, Allen GO, Gong F, Zhang Y, Hu JJ. Combined genetic and nutritional risk models of triple negative breast cancer. Nutr Cancer 2014; 66:955-63. [PMID: 25023197 DOI: 10.1080/01635581.2014.932397] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Triple negative breast cancer (TNBC) presents clinical challenges due to unknown etiology, lack of treatment targets, and poor prognosis. We examined combined genetic and nutritional risk models of TNBC in 354 breast cancer cases. We evaluated 18 DNA-repair nonsynonymous single nucleotide polymorphisms (nsSNPs) and dietary/nutritional intakes. Multivariate Adaptive Regression Splines models were used to select nutrients of interest and define cut-off values for logistic regression models. Our results suggest that TNBC was associated with 6 DNA-repair nsSNPs, ERCC4 R415Q (rs1800067), MSH3 R940Q (rs184967), MSH6 G39E (rs1042821), POLD1 R119H (rs1726801), XRCC1 R194W (rs1799782), and XPC A499V (rs2228000) and/or deficiencies in 3 micronutrients (zinc, folate, and β-carotene). Combined analyses of these 6 nsSNPs and 3 micronutrients showed significant association with TNBC: odds ratios = 2.77 (95% confidence interval = 1.01-7.64) and 10.89 (95% confidence interval = 3.50-33.89) for 2 and at least 3 risk factors, respectively. To the best of our knowledge, this is the first study to suggest that multiple genetic and nutritional factors are associated with TNBC, particularly in combination. Our findings, if validated in larger studies, will have important clinical implication that dietary modulations and/or micronutrient supplementations may prevent or reverse TNBC phenotype, so tumors can be treated with less toxic therapeutic strategies, particularly in genetically susceptible women.
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Affiliation(s)
- Eunkyung Lee
- a Department of Public Health Sciences and Sylvester Comprehensive Cancer Center , University of Miami Miller School of Medicine , Miami , Florida , USA
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Wang YD, Zhai WL, Wang HY, Xia XQ. An Updated Meta-analysis on the Association of X-Ray Repair Cross Complementing Group 1 Codon 399 Polymorphism with Hepatocellular Carcinoma Risk. Asian Pac J Cancer Prev 2014; 15:4443-8. [DOI: 10.7314/apjcp.2014.15.11.4443] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Peng Q, Lu Y, Lao X, Chen Z, Li R, Sui J, Qin X, Li S. Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis. Diagn Pathol 2014; 9:108. [PMID: 24893568 PMCID: PMC4064811 DOI: 10.1186/1746-1596-9-108] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2014] [Accepted: 05/21/2014] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND The base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent. METHODS We searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS A total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321, P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003-1.346, P=0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses. CONCLUSIONS The present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association. VIRTUAL SLIDES The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.
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Affiliation(s)
| | | | | | | | | | | | - Xue Qin
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
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Qin Q, Lu J, Zhu H, Xu L, Cheng H, Zhan L, Yang X, Zhang C, Sun X. PARP-1 Val762Ala polymorphism and risk of cancer: a meta-analysis based on 39 case-control studies. PLoS One 2014; 9:e98022. [PMID: 24853559 PMCID: PMC4031170 DOI: 10.1371/journal.pone.0098022] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Accepted: 04/27/2014] [Indexed: 12/18/2022] Open
Abstract
Background Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin-associated enzyme involved in several important cellular processes, particularly in the DNA repair system. PARP-1 rs1136410: C>T is among the most studied polymorphisms and likely involved in human carcinogenesis. However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this enzyme. Methodology and Principal Findings A comprehensive search was conducted in the PubMed and EMBASE databases until December 9, 2013. A total of 39 studies with 16,783 cancer cases and 23,063 control subjects were included in the meta-analysis on the basis of the inclusion and exclusion criteria. No significant association between the PARP-1 Val762Ala polymorphism and cancer risk was found when all of the studies were pooled into the analysis (VA + AA vs. VV: OR = 1.03, 95% CI = 0.95–1.11). The subgroup analysis of cancer types revealed that the –762Ala allele was associated with increased risk of gastric, cervical, and lung cancers and a decreased risk of glioma. In addition, a significantly increased risk of cancer associated with the polymorphism was observed in Asian descendents (VA + AA vs. VV: OR = 1.17, 95% CI = 1.09–1.25; AA vs. VV: OR = 1.28, 95% CI = 1.08–1.51; VA vs. VV: OR = 1.12, 95% CI = 1.04–1.20; AA vs. VA + VV: OR = 1.09, 95% CI = 1.03–1.39). These results also indicated that a joint effect between PARP-1 Val762Ala and XRCC1 Arg399Gln could be involved in the risk of cancer development (OR = 3.53, 95% CI = 1.30–9.59). Conclusion The present meta-analysis provides evidence that the PARP-1 Val762Ala may be involved in cancer development at least in some ethnic groups (Asian) or some specific cancer types (gastric, cervical, and lung cancers, and glioma).
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Affiliation(s)
- Qin Qin
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jing Lu
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Hongcheng Zhu
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Liping Xu
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Hongyan Cheng
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Liangliang Zhan
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Xi Yang
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Chi Zhang
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Xinchen Sun
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- * E-mail:
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Osorio A, Milne RL, Kuchenbaecker K, Vaclová T, Pita G, Alonso R, Peterlongo P, Blanco I, de la Hoya M, Duran M, Díez O, Ramón y Cajal T, Konstantopoulou I, Martínez-Bouzas C, Andrés Conejero R, Soucy P, McGuffog L, Barrowdale D, Lee A, SWE-BRCA, Arver B, Rantala J, Loman N, Ehrencrona H, Olopade OI, Beattie MS, Domchek SM, Nathanson K, Rebbeck TR, Arun BK, Karlan BY, Walsh C, Lester J, John EM, Whittemore AS, Daly MB, Southey M, Hopper J, Terry MB, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Steele L, Neuhausen SL, Ding YC, Hansen TVO, Jønson L, Ejlertsen B, Gerdes AM, Infante M, Herráez B, Moreno LT, Weitzel JN, Herzog J, Weeman K, Manoukian S, Peissel B, Zaffaroni D, Scuvera G, Bonanni B, Mariette F, Volorio S, Viel A, Varesco L, Papi L, Ottini L, Tibiletti MG, Radice P, Yannoukakos D, Garber J, Ellis S, Frost D, Platte R, Fineberg E, Evans G, Lalloo F, Izatt L, Eeles R, Adlard J, Davidson R, Cole T, Eccles D, Cook J, Hodgson S, Brewer C, Tischkowitz M, Douglas F, Porteous M, Side L, Walker L, Morrison P, Donaldson A, Kennedy J, Foo C, Godwin AK, Schmutzler RK, Wappenschmidt B, Rhiem K, Engel C, et alOsorio A, Milne RL, Kuchenbaecker K, Vaclová T, Pita G, Alonso R, Peterlongo P, Blanco I, de la Hoya M, Duran M, Díez O, Ramón y Cajal T, Konstantopoulou I, Martínez-Bouzas C, Andrés Conejero R, Soucy P, McGuffog L, Barrowdale D, Lee A, SWE-BRCA, Arver B, Rantala J, Loman N, Ehrencrona H, Olopade OI, Beattie MS, Domchek SM, Nathanson K, Rebbeck TR, Arun BK, Karlan BY, Walsh C, Lester J, John EM, Whittemore AS, Daly MB, Southey M, Hopper J, Terry MB, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Steele L, Neuhausen SL, Ding YC, Hansen TVO, Jønson L, Ejlertsen B, Gerdes AM, Infante M, Herráez B, Moreno LT, Weitzel JN, Herzog J, Weeman K, Manoukian S, Peissel B, Zaffaroni D, Scuvera G, Bonanni B, Mariette F, Volorio S, Viel A, Varesco L, Papi L, Ottini L, Tibiletti MG, Radice P, Yannoukakos D, Garber J, Ellis S, Frost D, Platte R, Fineberg E, Evans G, Lalloo F, Izatt L, Eeles R, Adlard J, Davidson R, Cole T, Eccles D, Cook J, Hodgson S, Brewer C, Tischkowitz M, Douglas F, Porteous M, Side L, Walker L, Morrison P, Donaldson A, Kennedy J, Foo C, Godwin AK, Schmutzler RK, Wappenschmidt B, Rhiem K, Engel C, Meindl A, Ditsch N, Arnold N, Plendl HJ, Niederacher D, Sutter C, Wang-Gohrke S, Steinemann D, Preisler-Adams S, Kast K, Varon-Mateeva R, Gehrig A, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S, Damiola F, Poppe B, Claes K, Piedmonte M, Tucker K, Backes F, Rodríguez G, Brewster W, Wakeley K, Rutherford T, Caldés T, Nevanlinna H, Aittomäki K, Rookus MA, van Os TAM, van der Kolk L, de Lange JL, Meijers-Heijboer HEJ, van der Hout AH, van Asperen CJ, Gómez Garcia EB, Hoogerbrugge N, Collée JM, van Deurzen CHM, van der Luijt RB, Devilee P, HEBON, Olah E, Lázaro C, Teulé A, Menéndez M, Jakubowska A, Cybulski C, Gronwald J, Lubinski J, Durda K, Jaworska-Bieniek K, Johannsson OT, Maugard C, Montagna M, Tognazzo S, Teixeira MR, Healey S, KConFab Investigators, Olswold C, Guidugli L, Lindor N, Slager S, Szabo CI, Vijai J, Robson M, Kauff N, Zhang L, Rau-Murthy R, Fink-Retter A, Singer CF, Rappaport C, Geschwantler Kaulich D, Pfeiler G, Tea MK, Berger A, Phelan CM, Greene MH, Mai PL, Lejbkowicz F, Andrulis I, Mulligan AM, Glendon G, Toland AE, Bojesen A, Pedersen IS, Sunde L, Thomassen M, Kruse TA, Jensen UB, Friedman E, Laitman Y, Shimon SP, Simard J, Easton DF, Offit K, Couch FJ, Chenevix-Trench G, Antoniou AC, Benitez J. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers. PLoS Genet 2014; 10:e1004256. [PMID: 24698998 PMCID: PMC3974638 DOI: 10.1371/journal.pgen.1004256] [Show More Authors] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Accepted: 02/04/2014] [Indexed: 12/20/2022] Open
Abstract
Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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Affiliation(s)
- Ana Osorio
- Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain
- Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain
| | - Roger L. Milne
- Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
| | - Karoline Kuchenbaecker
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Tereza Vaclová
- Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Guillermo Pita
- Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Rosario Alonso
- Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Paolo Peterlongo
- IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
| | - Ignacio Blanco
- Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain
| | - Miguel de la Hoya
- Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain
| | - Mercedes Duran
- Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain
| | - Orland Díez
- Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Institut de Recerca (VHIR), and Universitat Autonoma de Barcelona, Barcelona, Spain
| | | | - Irene Konstantopoulou
- Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece
| | - Cristina Martínez-Bouzas
- Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain
| | - Raquel Andrés Conejero
- Medical Oncology Service, Hospital Clínico Lozano Blesa, San Juan Bosco, Zaragoza, Spain
| | - Penny Soucy
- Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada
| | - Lesley McGuffog
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Daniel Barrowdale
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Andrew Lee
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - SWE-BRCA
- Department of Oncology, Lund University, Lund, Sweden
| | - Brita Arver
- Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
| | - Johanna Rantala
- Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
| | - Niklas Loman
- Department of Oncology, Lund University Hospital, Lund, Sweden
| | - Hans Ehrencrona
- Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
| | - Olufunmilayo I. Olopade
- Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois, United States of America
| | - Mary S. Beattie
- Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America
| | - Susan M. Domchek
- Abramson Cancer Center and Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
| | - Katherine Nathanson
- Abramson Cancer Center and Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
| | - Timothy R. Rebbeck
- Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America
| | - Banu K. Arun
- University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
| | - Beth Y. Karlan
- Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
| | - Christine Walsh
- Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
| | - Jenny Lester
- Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
| | - Esther M. John
- Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California, United States of America
| | - Alice S. Whittemore
- Department of Health Research & Policy, Stanford University School of Medicine, Stanford, California, United States of America
| | - Mary B. Daly
- Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America
| | - Melissa Southey
- Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Australia
| | - John Hopper
- Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia
| | - Mary B. Terry
- Department of Epidemiology, Columbia University, New York, New York, United States of America
| | - Saundra S. Buys
- Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
| | - Ramunas Janavicius
- Vilnius University Hospital Santariskiu Clinics, Hematology, oncology and transfusion medicine center, Department of Molecular and Regenerative Medicine, Vilnius, Lithuania
| | | | | | - Linda Steele
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Susan L. Neuhausen
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Yuan Chun Ding
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Thomas v. O. Hansen
- Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Lars Jønson
- Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Bent Ejlertsen
- Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Anne-Marie Gerdes
- Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Mar Infante
- Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain
| | - Belén Herráez
- Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain
| | | | - Jeffrey N. Weitzel
- Clinical Cancer Genetics, City of Hope, Duarte, California, United States of America
| | - Josef Herzog
- Clinical Cancer Genetics, City of Hope, Duarte, California, United States of America
| | - Kisa Weeman
- Clinical Cancer Genetics, City of Hope, Duarte, California, United States of America
| | - Siranoush Manoukian
- Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy
| | - Bernard Peissel
- Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy
| | - Daniela Zaffaroni
- Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy
| | - Giulietta Scuvera
- Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy
| | - Bernardo Bonanni
- Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy
| | - Frederique Mariette
- IFOM, Fondazione Istituto FIRC di Oncologia Molecolare and Cogentech Cancer Genetic Test Laboratory, Milan, Italy
| | - Sara Volorio
- IFOM, Fondazione Istituto FIRC di Oncologia Molecolare and Cogentech Cancer Genetic Test Laboratory, Milan, Italy
| | - Alessandra Viel
- Division of Experimental Oncology 1, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy
| | - Liliana Varesco
- Unit of Hereditary Cancer, Department of Epidemiology, Prevention and Special Functions, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
| | - Laura Papi
- Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Laura Ottini
- Department of Molecular Medicine, “Sapienza” University, Rome, Italy
| | | | - Paolo Radice
- Unit of Molecular bases of genetic risk and genetic testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy
| | - Drakoulis Yannoukakos
- Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece
| | - Judy Garber
- Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
| | - Steve Ellis
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Debra Frost
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Radka Platte
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Elena Fineberg
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Gareth Evans
- Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
| | - Fiona Lalloo
- Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
| | - Louise Izatt
- South East Thames Regional Genetics Service, Guy's Hospital London, United Kingdom
| | - Ros Eeles
- Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Julian Adlard
- Yorkshire Regional Genetics Service, Leeds, United Kingdom
| | - Rosemarie Davidson
- Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, United Kingdom
| | - Trevor Cole
- West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, United Kingdom
| | - Diana Eccles
- Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, United Kingdom
| | - Jackie Cook
- Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom
| | - Shirley Hodgson
- Clinical Genetics Department, St Georges Hospital, University of London, London, United Kingdom
| | - Carole Brewer
- Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, United Kingdom
| | - Marc Tischkowitz
- Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, United Kingdom
| | - Fiona Douglas
- Institute of Human Genetics, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
| | - Mary Porteous
- South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, United Kingdom
| | - Lucy Side
- North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom
| | - Lisa Walker
- Oxford Regional Genetics Service, Churchill Hospital, Oxford, United Kingdom
| | - Patrick Morrison
- Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, United Kingdom
| | - Alan Donaldson
- South West Regional Genetics Service, Bristol, United Kingdom
| | - John Kennedy
- Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin and St James's Hospital, Dublin, Eire
| | - Claire Foo
- Cheshire & Merseyside Clinical Genetics Service, Liverpool Women's NHS Foundation Trust, Liverpool, United Kingdom
| | - Andrew K. Godwin
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America
| | - Rita Katharina Schmutzler
- Centre of Familial Breast and Ovarian Cancer and Centre for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany
| | - Barbara Wappenschmidt
- Centre of Familial Breast and Ovarian Cancer and Centre for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany
| | - Kerstin Rhiem
- Centre of Familial Breast and Ovarian Cancer and Centre for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany
| | - Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - Alfons Meindl
- Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Nina Ditsch
- Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Norbert Arnold
- Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Hans Jörg Plendl
- Institute of Human Genetics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Dieter Niederacher
- Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Christian Sutter
- Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany
| | - Shan Wang-Gohrke
- Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany
| | - Doris Steinemann
- Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany
| | | | - Karin Kast
- Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
| | | | - Andrea Gehrig
- Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany
| | - Dominique Stoppa-Lyonnet
- Institut Curie, Department of Tumour Biology, Paris, France
- Institut Curie, INSERM U830, Paris, France
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Olga M. Sinilnikova
- Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon – Centre Léon Bérard, Lyon, France
- INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Sylvie Mazoyer
- INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Francesca Damiola
- INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Bruce Poppe
- Center for Medical Genetics, Ghent University, Ghent, Belgium
| | - Kathleen Claes
- Center for Medical Genetics, Ghent University, Ghent, Belgium
| | - Marion Piedmonte
- Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York, United States of America
| | | | - Floor Backes
- Ohio State University, Columbus Cancer Council, Columbus, Ohio, United States of America
| | - Gustavo Rodríguez
- Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois, United States of America
| | - Wendy Brewster
- Division of Gynecologic Oncology, NorthShore University HealthSystem, Chicago, Illinois, United States of America
| | - Katie Wakeley
- For Tufts Medical Center, Boston, Massachusetts, United States of America
| | - Thomas Rutherford
- Yale University School of Medicine, New Haven, Connecticut, United States of America
| | - Trinidad Caldés
- Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain
| | - Heli Nevanlinna
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
| | - Kristiina Aittomäki
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
| | - Matti A. Rookus
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Theo A. M. van Os
- Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
| | - Lizet van der Kolk
- Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - J. L. de Lange
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | - A. H. van der Hout
- University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - Christi J. van Asperen
- Department of Clinical Genetics, Leiden University Medical Center Leiden, Leiden, The Netherlands
| | - Encarna B. Gómez Garcia
- Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands
| | - Nicoline Hoogerbrugge
- Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - J. Margriet Collée
- Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Carolien H. M. van Deurzen
- Department of Pathology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Rob B. van der Luijt
- Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Peter Devilee
- Department of Human Genetics & Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - HEBON
- The Hereditary Breast and Ovarian Cancer Research Group, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Edith Olah
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
| | - Conxi Lázaro
- Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain
| | - Alex Teulé
- Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain
| | - Mireia Menéndez
- Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain
| | - Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
| | - Cezary Cybulski
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
| | - Jacek Gronwald
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
| | - Jan Lubinski
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
| | - Katarzyna Durda
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
| | - Katarzyna Jaworska-Bieniek
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
- Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland
| | - Oskar Th. Johannsson
- Department of Oncology, Landspitali University Hospital and BMC, Faculty of Medicine, University of Iceland, Reykjavik Iceland
| | - Christine Maugard
- Laboratoire de Diagnostic Génétique et Service d'Onco-hématologie, Hopitaux Universitaire de Strasbourg, CHRU Nouvel Hôpital Civil, Strasbourg, France
| | - Marco Montagna
- Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Silvia Tognazzo
- Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Manuel R. Teixeira
- Department of Genetics, Portuguese Oncology Institute, Porto, and Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal
| | - Sue Healey
- Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, Australia
| | - KConFab Investigators
- Kathleen Cuningham Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Center, Melbourne, Australia
| | - Curtis Olswold
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Lucia Guidugli
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Noralane Lindor
- Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America
| | - Susan Slager
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Csilla I. Szabo
- Center for Translational Cancer Research, Department of Biological Sciences, University of Delaware, Newark, Delaware, United States of America
| | - Joseph Vijai
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
- Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
| | - Mark Robson
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
| | - Noah Kauff
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
| | - Liying Zhang
- Diagnostic Molecular Genetics Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
| | - Rohini Rau-Murthy
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
| | - Anneliese Fink-Retter
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Christian F. Singer
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Christine Rappaport
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | | | - Georg Pfeiler
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Muy-Kheng Tea
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Andreas Berger
- Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Catherine M. Phelan
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America
| | - Mark H. Greene
- Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Phuong L. Mai
- Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | | | - Irene Andrulis
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, and Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Anna Marie Mulligan
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
| | - Gord Glendon
- Ontario Cancer Genetics Network: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Amanda Ewart Toland
- Division of Human Cancer Genetics, Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America
| | - Anders Bojesen
- Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark
| | - Inge Sokilde Pedersen
- Section of Molecular Diagnostics, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
| | - Lone Sunde
- Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
| | - Mads Thomassen
- Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
| | - Torben A. Kruse
- Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
| | - Uffe Birk Jensen
- Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
| | | | | | | | - Jacques Simard
- Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada
| | - Douglas F. Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Kenneth Offit
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
- Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
| | - Fergus J. Couch
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Georgia Chenevix-Trench
- Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, Australia
| | - Antonis C. Antoniou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Javier Benitez
- Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain
- Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain
- Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain
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Kim WC, Ma C, Li WM, Chohan M, Wilson III DM, Lee CH. Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population. PLoS One 2014; 9:e90837. [PMID: 24595156 PMCID: PMC3942487 DOI: 10.1371/journal.pone.0090837] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Accepted: 02/05/2014] [Indexed: 11/30/2022] Open
Abstract
Apurinic/apyrimidinic endonuclease 1 (APE1) is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5′ to abasic sites. APE1 also has 3′-5′ DNA exonuclease and 3′ DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76–85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3′ of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60–80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.
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Affiliation(s)
- Wan Cheol Kim
- Chemistry Program, University of Northern British Columbia, Prince George, British Columbia, Canada
| | - Conan Ma
- Chemistry Program, University of Northern British Columbia, Prince George, British Columbia, Canada
| | - Wai-Ming Li
- Chemistry Program, University of Northern British Columbia, Prince George, British Columbia, Canada
| | - Manbir Chohan
- Chemistry Program, University of Northern British Columbia, Prince George, British Columbia, Canada
| | - David M. Wilson III
- Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
| | - Chow H. Lee
- Chemistry Program, University of Northern British Columbia, Prince George, British Columbia, Canada
- * E-mail:
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Roszak A, Lianeri M, Sowińska A, Jagodziński PP. Involvement of PARP-1 Val762Ala polymorphism in the onset of cervical cancer in caucasian women. Mol Diagn Ther 2014; 17:239-45. [PMID: 23633189 PMCID: PMC3715681 DOI: 10.1007/s40291-013-0036-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND OBJECTIVE Data on the Val762Ala (rs1136410) polymorphism in the poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP-1) gene as a risk factor for various types of cancers in different ethnicities are inconsistent. We studied this association in a Caucasian population. METHODS Using high-resolution melting curve analysis (HRM), we studied the distribution of the PARP-1 Val762Ala polymorphism in patients with cervical cancer (n = 446) and in controls (n = 491). RESULTS Logistic regression analysis adjusting for age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal status demonstrated that the PARP-1 Val762Ala polymorphism was associated with an increased risk of cervical cancer. The adjusted odds ratio (OR) for patients with the Ala/Val genotype versus the Val/Val genotype was 1.381 (95 % CI = 1.025-1.859, p = 0.033), and the adjusted OR for the Ala/Ala or Ala/Val genotype versus the Val/Val genotype was 1.403 (95 % CI = 1.057-1.863, p = 0.019). The p value from the chi-square test of the trend observed for the PARP-1 Val762Ala polymorphism was statistically significant (p trend = 0.0123). Stratified analyses of the PARP-1 Val762Ala genotype distribution and cervical cancer risk showed that the age-adjusted OR of Ala/Ala or Ala/Val vs Val/Val for pregnancy was 1.388 (95 % CI = 1.027-1.877, p = 0.0328), 1.773 (95 % CI = 1.145-2.745, p = 0.0100) for contraceptive use, and 1.604 (95 % CI = 1.132-2.272, p = 0.0077) for postmenopausal women. The age-adjusted OR of Ala/Val vs Val/Val for contraceptive use was 1.769 (95 % CI = 1.114-2.809, p = 0.0154) and for postmenopausal women was 1.577 (95 % CI = 1.094-2.272, p = 0.0143). CONCLUSION Our studies suggest that the PARP-1 Val762Ala polymorphism may be a genetic risk factor for cervical cancer.
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Affiliation(s)
- Andrzej Roszak
- Department of Radiotherapy and Gynecological Oncology, Greater Poland Cancer Center Poznan, Poznan, Poland
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Bu T, Liu L, Sun Y, Zhao L, Peng Y, Zhou S, Li L, Chen S, Gao Y. XRCC1 Arg399Gln polymorphism confers risk of breast cancer in American population: a meta-analysis of 10846 cases and 11723 controls. PLoS One 2014; 9:e86086. [PMID: 24489692 PMCID: PMC3904848 DOI: 10.1371/journal.pone.0086086] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2013] [Accepted: 12/09/2013] [Indexed: 11/30/2022] Open
Abstract
Background In the X-ray repair cross-complementing group 1 (XRCC1) gene, a polymorphism, Arg399Gln (rs25487), has been shown to change neoconservative amino acid and thus result in alternation of DNA repair capacity. Numerous studies have investigated the association between Arg399Gln and breast cancer risk in the American population, but yielding inconsistent results. This study aimed to clarify the role of this polymorphism in susceptibility to breast cancer. Methods Literatures were searched in multiple databases including PubMed, Springer Link, Ovid, EBSCO and ScienceDirect databases up to April 2013. A comprehensive meta-analysis was conducted to estimate the overall odds ratio (OR), by integrating data from 18 case control studies of 10846 cases and 11723 controls in the American population. Results Overall, significant association was observed between the Arg399Gln polymorphism and breast cancer risk under the random-effects model (OR for dominant model = 1.12, 95% CI: 1.02–1.24, Pheterogeneity = 0.003; OR for additive model = 1.07, 95% CI: 1.01–1.14, Pheterogeneity = 0.017). Further sensitivity analysis supported the robust stability of this current result by showing similar ORs before and after removal of a single study. Conclusions This meta-analysis suggests that the XRCC1 Arg399Gln polymorphism may significantly contribute to susceptibility of breast cancer in the American population.
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Affiliation(s)
- Tao Bu
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
- Department of Prevention and Health Care, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Li Liu
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yong Sun
- Department of Prevention and Health Care, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Li Zhao
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yang Peng
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
| | - Shudong Zhou
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
| | - Lixia Li
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
| | - Sidong Chen
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
- * E-mail: (SD); (YG)
| | - Yanhui Gao
- Department of Epidemiology and Biostatistics, School of Public Health and Guangdong Key Lab of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
- * E-mail: (SD); (YG)
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Hua RX, Li HP, Liang YB, Zhu JH, Zhang B, Ye S, Dai QS, Xiong SQ, Gu Y, Sun XZ. Association between the PARP1 Val762Ala polymorphism and cancer risk: evidence from 43 studies. PLoS One 2014; 9:e87057. [PMID: 24489833 PMCID: PMC3904982 DOI: 10.1371/journal.pone.0087057] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Accepted: 12/18/2013] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in the detection and repair of damaged DNA, as well as cell proliferation and death. Numerous studies have examined the associations between PARP1 Val762Ala (rs1136410 T>C) polymorphism and cancer susceptibility; nevertheless, the findings from different research groups remain controversial. METHODS We searched literatures from MEDLINE, EMBASE and CBM pertaining to such associations, and then calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using random-effects model. The false-positive report probability (FPRP) analysis was used to confirm the validity of significant findings. Moreover, potential effects of rs1136410 variants on PARP1 mRNA expression were analyzed for three ethnicities by combining data from HapMap (genotype) and SNPexp (mRNA expression). RESULTS The final meta-analysis incorporated 43 studies, consisting of 17,351 cases and 22,401 controls. Overall, our results did not suggest significant associations between Ala variant (Ala/Ala or Ala/Val genotype) and cancer risk. However, further stratification analysis showed significantly increased risk for gastric cancer (Ala/Ala vs. Val/Val: OR = 1.56, 95% CI = 1.01-2.42, Ala/Val vs. Val/Val: OR = 1.34, 95% CI = 1.14-1.58, dominant model: OR = 1.41, 95% CI = 1.21-1.65 and Ala vs. Val: OR = 1.29, 95% CI = 1.07-1.55). On the contrary, decreased risk for brain tumor (Ala/Val vs. Val/Val: OR = 0.77, 95% CI = 0.68-0.87, dominant model: OR = 0.77, 95% CI = 0.68-0.87 and Ala vs. Val: OR = 0.82, 95% CI = 0.74-0.91). Additionally, we found that the Ala carriers had a significantly increased risk in all models for Asians. Our mRNA expression data provided further biological evidence to consolidate this finding. CONCLUSIONS Despite some limitations, this meta-analysis found evidence for an association between the PAPR1 Val762Ala and cancer susceptibility within gastric cancer, brain tumor and Asian subgroups.
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Affiliation(s)
- Rui-Xi Hua
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - He-Ping Li
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yan-Bing Liang
- General Department of Internal Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jin-Hong Zhu
- Department of Molecular Epidemiology and Laboratory Medicine, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
| | - Bing Zhang
- Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sheng Ye
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiang-Sheng Dai
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shi-Qiu Xiong
- Department of Pathology, University of Cambridge, Cambridge, United Kingdom
| | - Yong Gu
- Department of Thoracic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- * E-mail: (YG); (X-ZS)
| | - Xiang-Zhou Sun
- Department of Urinary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- * E-mail: (YG); (X-ZS)
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The association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility: a meta-analysis based on case–control studies. Tumour Biol 2014; 35:4727-34. [DOI: 10.1007/s13277-014-1618-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Accepted: 01/03/2014] [Indexed: 01/11/2023] Open
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APEX nuclease (multifunctional DNA repair enzyme) 1 gene Asp148Glu polymorphism and cancer risk: a meta-analysis involving 58 articles and 48903 participants. PLoS One 2013; 8:e83527. [PMID: 24349526 PMCID: PMC3861501 DOI: 10.1371/journal.pone.0083527] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 11/05/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Polymorphisms in the APEX nuclease (multifunctional DNA repair enzyme) 1 gene (APEX1) may be involved in the carcinogenesis by affecting DNA repair. We aimed to summarize available data on the association of the APEX1 Asp148Glu (rs1130409) polymorphism with risk of multiple types of cancer via a meta-analysis. METHODS AND RESULTS In total, 58 qualified articles including 22,398 cancer patients and 26,505 controls were analyzed, and the data were extracted independently by two investigators. Analyses of the full data set indicated a marginally significant association of the APEX1 Asp148Glu polymorphism with cancer risk under allelic (odds ratio (OR)=1.05; 95% confidence interval (95% CI): 0.99-1.11; P=0.071), dominant (OR=1.09; 95% CI: 1.01-1.17; P=0.028), and heterozygous genotypic (OR=1.08; 95% CI: 1.01-1.16; P=0.026) models, with significant heterogeneity and publication bias. In subgroup analyses by cancer type, with a Bonferroni corrected alpha of 0.05/6, significant association was observed for gastric cancer under both dominant (OR=1.74; 95% CI: 1.2-2.51; P=0.003) and heterozygous genotypic (OR=1.66; 95% CI: 1.2-2.31; P=0.002) models. In subgroup analysis by ethnicity, risk estimates were augmented in Caucasians, especially under dominant (OR=1.11; 95% CI: 1.0-1.24; P=0.049) and heterozygous genotypic (OR=1.11; 95% CI: 0.99-1.24; P=0.063) models. By study design, there were no significant differences between population-based and hospital-based studies. In subgroup analysis by sample size, risk estimates were remarkably overestimated in small studies, and no significance was reached in large studies except under the heterozygous genotypic model (OR=1.23; 95% CI: 1.06-1.43; P=0.006, significant at a Bonferroni corrected alpha of 0.05/2). By quality score, the risk estimates, albeit nonsignificant, were higher in low-quality studies than in high-quality studies. Further meta-regression analyses failed to identify any contributory confounders for the associated risk estimates. CONCLUSIONS Our findings suggest that APEX1 Asp148Glu polymorphism might be a genetic risk factor for the development of gastric cancer. Further investigations on large populations are warranted.
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Association of X-ray repair cross complementing group 1 Arg399Gln polymorphisms with the risk of squamous cell carcinoma of the head and neck: evidence from an updated meta-analysis. PLoS One 2013; 8:e77898. [PMID: 24205020 PMCID: PMC3813759 DOI: 10.1371/journal.pone.0077898] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 09/05/2013] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Epidemiologic studies have reported the association of X-ray repair cross-complementary group 1 (XRCC1) Arg399Gln polymorphisms with susceptibility to squamous cell carcinoma of the head and neck (HNSCC). However, the results were conflictive rather than conclusive. The purpose of this study was to clarify the association of XRCC1 Arg399Gln variants with HNSCC risk. METHODS Systematic searches were performed through the search engines of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database. Summary odds ratio (OR) with 95% confidence intervals (CI) was computed to estimate the strength association. RESULTS Overall, we did not observe any association of XRCC1 Arg399Gln polymorphisms with HNSCC risk in total population (OR = 0.95, 95% CI: 0.76-1.19 for Gln/Gln vs. Arg/Arg, OR = 1.05, 95% CI: 0.92-1.20 for Arg/Gln vs. Arg/Arg, and OR = 1.03, 95% CI: 0.90-1.18 for Gln/Gln+Arg/Gln vs. Arg/Arg) based on 18 studies including 3917 cases and 4560 controls. In subgroup analyses, we observed an increased risk of XRCC1 399 Arg/Gln genotype for HNSCC in Caucasians (OR = 1.20, 95% CI: 1.00-1.44) and Gln/Gln genotype for larynx squamous cell carcinoma (OR = 1.63, 95% CI: 1.10-2.40). We did not observe any association between XRCC1 Arg399Gln variants and HNSCC risk in additional subgroup analyses. CONCLUSION The results from this present meta-analysis suggest that XRCC1 Arg399Gln variants may contribute to HNSCC risk among Caucasians and to the risk of larynx squamous cell carcinoma. Further, well-designed studies with larger sample sizes are required to verify our findings.
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Li S, Deng Y, You JP, Chen ZP, Peng QL, Huang XM, Lu QH, Huang XL, Zhao JM, Qin X. XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms in esophageal cancer risk: a meta-analysis. Dig Dis Sci 2013; 58:1880-90. [PMID: 23543084 DOI: 10.1007/s10620-013-2569-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Accepted: 01/06/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. AIM To elucidate the role of XRCC1 Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all available studies were considered in the present meta-analysis. METHODS Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. RESULTS According to the inclusion criteria and exclusion criteria, a total of 21 eligible studies were included in the pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11 described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis suggested that there was no evidence of significant association between XRCC1 Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal cancer, the results showed that Arg399Gln polymorphism was not associated with esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1 Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His genotypes were not significantly associated with increased risk of EC. A similar negative association was maintained in dominant and recessive models. However, for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the variant genotype Trp/Trp had a significant increased risk of esophageal cancer (OR = 1.295, 95 % CI 1.053-1.591, P = 0.014). In addition, increased associations were found in recessive model (OR = 1.332, 95 % CI 1.093-1.624, P = 0.005). CONCLUSIONS Our meta-analysis suggested that Arg194Trp Trp allele might act as a risk allele in its association with esophageal cancer.
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Affiliation(s)
- Shan Li
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
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